{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:28:31Z","timestamp":1760228911267,"version":"build-2065373602"},"reference-count":96,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft, Collaborative Research Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Cytomegaloviruses (CMVs) are controlled by innate and adaptive immune responses in an immunocompetent host while causing multiple organ diseases in an immunocompromised host. A risk group of high clinical relevance comprises transiently immunocompromised recipients of hematopoietic cell transplantation (HCT) in the \u201cwindow of risk\u201d between eradicative therapy of hematopoietic malignancies and complete reconstitution of the immune system. Cellular immunotherapy by adoptive transfer of CMV-specific CD8 T cells is an option to prevent CMV disease by controlling a primary or reactivated infection. While experimental models have revealed a viral epitope-specific antiviral function of cognate CD8 T cells, the site at which control is exerted remained unidentified. The observation that remarkably few transferred cells protect all organs may indicate an early blockade of virus dissemination from a primary site of productive infection to various target organs. Alternatively, it could indicate clonal expansion of a few transferred CD8 T cells for preventing intra-tissue virus spread after successful initial organ colonization. Our data in the mouse model of murine CMV infection provide evidence in support of the second hypothesis. We show that transferred cells vigorously proliferate to prevent virus spread, and thus viral histopathology, by confining and eventually resolving tissue infection within nodular inflammatory foci.<\/jats:p>","DOI":"10.3390\/v14061145","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T05:25:42Z","timestamp":1653974742000},"page":"1145","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Memory CD8 T Cells Protect against Cytomegalovirus Disease by Formation of Nodular Inflammatory Foci Preventing Intra-Tissue Virus Spread"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5767-5111","authenticated-orcid":false,"given":"Rafaela","family":"Holtappels","sequence":"first","affiliation":[{"name":"Institute for Virology and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7062-9088","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Podlech","sequence":"additional","affiliation":[{"name":"Institute for Virology and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsten","family":"Freitag","sequence":"additional","affiliation":[{"name":"Institute for Virology and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9190-6497","authenticated-orcid":false,"given":"Niels A.","family":"Lemmermann","sequence":"additional","affiliation":[{"name":"Institute for Virology and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias J.","family":"Reddehase","sequence":"additional","affiliation":[{"name":"Institute for Virology and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Comparative genomics of primate cytomegaloviruses","volume":"Volume 1","author":"Reddehase","year":"2013","journal-title":"Cytomegaloviruses: From Molecular Pathogenesis to Intervention"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"435","DOI":"10.3181\/00379727-86-21123","article-title":"Propagation of salivary gland virus of the mouse in tissue cultures","volume":"86","author":"Smith","year":"1954","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"424","DOI":"10.3181\/00379727-92-22498","article-title":"Propagation in tissue cultures of a cytopathogenic virus from human salivary gland virus (SGV) disease","volume":"92","author":"Smith","year":"1956","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s00430-015-0400-7","article-title":"Stepwise adaptation of murine cytomegalovirus to cells of a foreign host for identification of host range determinants","volume":"204","author":"Ostermann","year":"2015","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1093\/infdis\/171.6.1599","article-title":"Dramatic interstrain differences in the replication of human cytomegalovirus in SCID-hu mice","volume":"171","author":"Brown","year":"1995","journal-title":"J. Infect. Dis."},{"key":"ref_6","first-page":"417","article-title":"Humanized mouse models of cytomegalovirus pathogenesis and latency","volume":"Volume 1","author":"Reddehase","year":"2013","journal-title":"Cytomegaloviruses: From Molecular Pathogenesis to Intervention"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.coviro.2015.06.006","article-title":"Humanized mouse models of human cytomegalovirus infection","volume":"13","author":"Crawford","year":"2015","journal-title":"Curr. Opin. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Reddehase, M.J., and Lemmermann, N.A.W. (2018). Mouse model of cytomegalovirus disease and immunotherapy in the immunocompromised host: Predictions for medical translation that survived the \u201ctest of time\u201d. Viruses, 10.","DOI":"10.3390\/v10120693"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s00430-007-0073-y","article-title":"Rhesus CMV: An emerging animal model for human CMV","volume":"197","author":"Powers","year":"2008","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s00430-008-0074-5","article-title":"Evaluation of recombinant modified vaccinia Ankara virus-based rhesus cytomegalovirus vaccines in rhesus macaques","volume":"197","author":"Yue","year":"2008","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_11","first-page":"461","article-title":"Non-human-primate models of cytomegalovirus infection, prevention, and therapy","volume":"Volume 2","author":"Reddehase","year":"2013","journal-title":"Cytomegaloviruses: From Molecular Pathogenesis to Intervention"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.3390\/v6041483","article-title":"Using the nonhuman primate model of HCMV to guide vaccine development","volume":"6","author":"Deere","year":"2014","journal-title":"Viruses"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.coviro.2017.08.005","article-title":"Rhesus monkeys for a nonhuman primate model of cytomegalovirus infections","volume":"25","author":"Itell","year":"2017","journal-title":"Curr. Opin. Virol."},{"key":"ref_14","first-page":"88","article-title":"The Guinea pig model of congenital cytomegalovirus infection","volume":"Volume 2","author":"Reddehase","year":"2013","journal-title":"Cytomegaloviruses: From Molecular Pathogenesis to Intervention"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/cmi.2014.51","article-title":"Immunobiology of congenital cytomegalovirus infection of the central nervous system\u2014The murine cytomegalovirus model","volume":"12","author":"Slavuljica","year":"2015","journal-title":"Cell. Mol. Immunol."},{"key":"ref_16","first-page":"312","article-title":"The rat model of cytomegalovirus infection and vascular disease","volume":"Volume 2","author":"Reddehase","year":"2013","journal-title":"Cytomegaloviruses: From Molecular Pathogenesis to Intervention"},{"key":"ref_17","first-page":"310","article-title":"Host genetic models in cytomegalovirus immunology","volume":"Volume 2","author":"Reddehase","year":"2013","journal-title":"Cytomegaloviruses: From Molecular Pathogenesis to Intervention"},{"key":"ref_18","first-page":"38","article-title":"Manipulating CMV genomes by BAC mutagenesis: Strategies and applications","volume":"Volume 1","author":"Reddehase","year":"2013","journal-title":"Cytomegaloviruses: From Molecular Pathogenesis to Intervention"},{"key":"ref_19","first-page":"812742","article-title":"Reverse genetics modification of cytomegalovirus antigenicity and immunogenicity by CD8 T-cell epitope deletion and insertion","volume":"2011","author":"Lemmermann","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_20","first-page":"23","article-title":"Molecular evolution of murine cytomegalovirus genomes","volume":"Volume 1","author":"Reddehase","year":"2013","journal-title":"Cytomegaloviruses: From Molecular Pathogenesis to Intervention"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1099\/0022-1317-72-9-2059","article-title":"Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells","volume":"72","author":"Sissons","year":"1991","journal-title":"J. Gen. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11879","DOI":"10.1073\/pnas.91.25.11879","article-title":"Human cytomegalovirus latent infection of granulocyte-macrophage progenitors","volume":"91","author":"Kondo","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.1073\/pnas.95.7.3937","article-title":"Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells","volume":"95","author":"Hahn","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4806","DOI":"10.1128\/JVI.73.6.4806-4812.1999","article-title":"Quantitative analysis of latent human cytomegalovirus","volume":"73","author":"Slobedman","year":"1999","journal-title":"J. Virol."},{"key":"ref_25","first-page":"330","article-title":"Epigenetic regulation of human cytomegalovirus gene expression: Impact on latency and reactivation","volume":"Volume 1","author":"Reddehase","year":"2013","journal-title":"Cytomegaloviruses: From Molecular Pathogenesis to Intervention"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s00430-015-0401-6","article-title":"Sleepless latency of human cytomegalovirus","volume":"204","author":"Poole","year":"2015","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1146\/annurev-virology-110615-042422","article-title":"Human cytomegalovirus latency: Approaching the Gordian Knot","volume":"3","author":"Goodrum","year":"2016","journal-title":"Annu. Rev. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e00013-18","DOI":"10.1128\/mBio.00013-18","article-title":"Defining the transcriptional landscape during cytomegalovirus latency with single-cell RNA sequencing","volume":"9","author":"Shnayder","year":"2018","journal-title":"mBio"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s00430-019-00581-1","article-title":"HCMV latency: What regulates the regulators?","volume":"208","author":"Elder","year":"2019","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"668885","DOI":"10.3389\/fimmu.2021.668885","article-title":"Stochastic episodes of latent cytomegalovirus transcription drive CD8 T-cell \u201cmemory inflation\u201d and avoid immune evasion","volume":"12","author":"Griessl","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/267721a0","article-title":"Reactivation of murine cytomegalovirus by cyclophosphamide","volume":"267","author":"Mayo","year":"1977","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5360","DOI":"10.1128\/jvi.67.9.5360-5366.1993","article-title":"Lungs are a major organ site of cytomegalovirus latency and recurrence","volume":"67","author":"Balthesen","year":"1993","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0092-8674(01)80014-3","article-title":"Reactivation of latent human cytomegalovirus by allogeneic stimulation of blood cells from healthy donors","volume":"91","author":"Fish","year":"1997","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.chom.2010.08.001","article-title":"Granulocyte-colony stimulating factor reactivates human cytomegalovirus in a latently infected humanized mouse model","volume":"8","author":"Smith","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.bbmt.2013.10.019","article-title":"HCMV infection of humanized mice after transplantation of G-CSF-mobilized peripheral blood stem cells from HCMV-seropositive donors","volume":"20","author":"Hakki","year":"2014","journal-title":"Biol. Blood Marrow. Transpl."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0065-3527(08)60073-1","article-title":"Cell types involved in replication and distribution of human cytomegalovirus","volume":"46","author":"Plachter","year":"1996","journal-title":"Adv. Virus Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1099\/0022-1317-79-9-2099","article-title":"Reconstitution of CD8 T cells is essential for the prevention of multiple-organ cytomegalovirus histopathology after bone marrow transplantation","volume":"79","author":"Podlech","year":"1998","journal-title":"J. Gen. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/s41579-021-00582-z","article-title":"Pathogenesis of human cytomegalovirus in the immunocompromised host","volume":"19","author":"Griffiths","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s00430-019-00582-0","article-title":"Coevolution pays off: Herpesviruses have the license to escape the DNA sensing pathway","volume":"208","author":"Stempel","year":"2019","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.coviro.2015.07.001","article-title":"NK cell interplay with cytomegaloviruses","volume":"15","year":"2015","journal-title":"Curr. Opin. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41577-019-0225-5","article-title":"Modulation of innate and adaptive immunity by cytomegaloviruses","volume":"20","author":"Berry","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0165-2478(97)00073-4","article-title":"Cytomegaloviruses use multiple mechanisms to elude the host immune response","volume":"57","author":"Wiertz","year":"1997","journal-title":"Immunol. Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1600-065X.1999.tb01291.x","article-title":"Cytomegaloviral control of MHC class I function in the mouse","volume":"168","author":"Hengel","year":"1999","journal-title":"Immunol. Rev."},{"key":"ref_44","first-page":"333","article-title":"Cytomegalovirus immune evasion","volume":"325","author":"Powers","year":"2008","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s00430-008-0089-y","article-title":"MHC class I immune evasion in MCMV infection","volume":"197","author":"Doom","year":"2008","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Becker, S., Fink, A., Podlech, J., Reddehase, M.J., and Lemmermann, N.A. (2022). Host-adapted gene families involved in murine cytomegalovirus immune evasion. Viruses, 14.","DOI":"10.3390\/v14010128"},{"key":"ref_47","first-page":"26","article-title":"The epidemiology and public health impact of congenital cytomegalovirus infection","volume":"Volume 2","author":"Reddehase","year":"2013","journal-title":"Cytomegaloviruses: From Molecular Pathogenesis to Intervention"},{"key":"ref_48","first-page":"55","article-title":"Clinical cytomegalovirus research: Congenital infection","volume":"Volume 2","author":"Reddehase","year":"2013","journal-title":"Cytomegaloviruses: From Molecular Pathogenesis to Intervention"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1056\/NEJM197511272932201","article-title":"The transplanted kidney as a source of cytomegalovirus infection","volume":"293","author":"Ho","year":"1975","journal-title":"N. Engl. J Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1056\/NEJM198605293142205","article-title":"Acquisition of donor strains of cytomegalovirus by renal-transplant recipients","volume":"314","author":"Chou","year":"1986","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/S0140-6736(88)90685-X","article-title":"Symptomatic cytomegalovirus infection in seropositive kidney recipients: Reinfection with donor virus rather than reactivation of recipient virus","volume":"2","author":"Grundy","year":"1988","journal-title":"Lancet"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1159\/000061707","article-title":"Relative importance of cytomegalovirus load as a risk factor for cytomegalovirus disease in the immunocompromised host","volume":"21","author":"Emery","year":"1998","journal-title":"Monogr. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s00430-019-00592-y","article-title":"Cellular reservoirs of latent cytomegaloviruses","volume":"208","author":"Reddehase","year":"2019","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"294","DOI":"10.3389\/fimmu.2016.00294","article-title":"Mutual interference between cytomegalovirus and reconstitution of protective immunity after hematopoietic cell transplantation","volume":"7","author":"Reddehase","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Reddehase, M.J., Holtappels, R., and Lemmermann, N.A.W. (2021). Consequence of histoincompatibility beyond GvH-reaction in cytomegalovirus disease associated with allogeneic hematopoietic cell transplantation: Change of paradigm. Viruses, 13.","DOI":"10.3390\/v13081530"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Hamdan, S., Reddehase, M.J., and Holtappels, R. (2022). Cytomegalovirus immune evasion sets the functional avidity threshold for protection by CD8 T cells. Med. Microbiol. Immunol.","DOI":"10.1007\/s00430-022-00733-w"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.3389\/fmicb.2019.01186","article-title":"Human cytomegalovirus latency and reactivation in allogeneic hematopoietic stem cell transplant recipients","volume":"10","author":"Stern","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_58","first-page":"S19","article-title":"The lung as a critical organ in marrow transplantation","volume":"14","author":"Quabeck","year":"1994","journal-title":"Bone Marrow Transplant."},{"key":"ref_59","first-page":"199","article-title":"Pathogenesis of cytomegalovirus pneumonia in immunocompromised hosts","volume":"10","author":"Riddell","year":"1995","journal-title":"Semin. Respir. Infect."},{"key":"ref_60","first-page":"337","article-title":"Clinical cytomegalovirus research: Hematopoietic cell transplantation","volume":"Volume 2","author":"Reddehase","year":"2013","journal-title":"Cytomegaloviruses: From Molecular Pathogenesis to Intervention"},{"key":"ref_61","first-page":"402","article-title":"Antiviral therapy, drug resistance and computed resistance profiling","volume":"Volume 2","author":"Reddehase","year":"2013","journal-title":"Cytomegaloviruses: From Molecular Pathogenesis to Intervention"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1093\/cid\/ciy696","article-title":"Definitions of resistant and refractory cytomegalovirus infection and disease in transplant recipients for use in clinical trials","volume":"68","author":"Chemaly","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1128\/jvi.55.2.264-273.1985","article-title":"Interstitial murine cytomegalovirus pneumonia after irradiation: Characterization of cells that limit viral replication during established infection of the lungs","volume":"55","author":"Reddehase","year":"1985","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00430-008-0093-2","article-title":"CD8 T-cell based immunotherapy of cytomegalovirus infection: \u201cproof of concept\u201d provided by the murine model","volume":"197","author":"Holtappels","year":"2008","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s00430-012-0258-x","article-title":"Parameters determining the efficacy of adoptive CD8 T-cell therapy of cytomegalovirus infection","volume":"201","author":"Ebert","year":"2012","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1126\/science.1352912","article-title":"Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones","volume":"257","author":"Riddell","year":"1992","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1056\/NEJM199510193331603","article-title":"Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor","volume":"333","author":"Walter","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3916","DOI":"10.1182\/blood.V99.11.3916","article-title":"Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy","volume":"99","author":"Einsele","year":"2002","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4360","DOI":"10.1182\/blood-2010-01-262089","article-title":"Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation","volume":"116","author":"Feuchtinger","year":"2010","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1097\/CJI.0b013e31824300a2","article-title":"Adoptive immunotherapy with CMV-specific cytotoxic T lymphocytes for stem cell transplant patients with refractory CMV infections","volume":"35","author":"Bao","year":"2012","journal-title":"J. Immunother."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.jcyt.2014.05.023","article-title":"Clinical-scale isolation of \u2018minimally manipulated\u2019 cytomegalovirus-specific donor lymphocytes for the treatment of refractory cytomegalovirus disease","volume":"16","author":"Odendahl","year":"2014","journal-title":"Cytotherapy"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1093\/infdis\/jix357","article-title":"Cytomegalovirus-specific T-cell transfer for refractory cytomegalovirus infection after haploidentical stem cell transplantation: The quantitative and qualitative immune recovery for cytomegalovirus","volume":"216","author":"Pei","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13045-019-0701-1","article-title":"Strategies of adoptive T -cell transfer to treat refractory viral infections post allogeneic stem cell transplantation","volume":"12","author":"Kaeuferle","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5400","DOI":"10.1128\/JVI.79.9.5400-5413.2005","article-title":"Highly protective in vivo function of cytomegalovirus IE1 epitope-specific memory CD8 T cells purified by T-cell receptor-based cell sorting","volume":"79","author":"Juelch","year":"2005","journal-title":"J. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00430-008-0092-3","article-title":"Epitope-specific in vivo protection against cytomegalovirus disease by CD8 T cells in the murine model of preemptive immunotherapy","volume":"197","author":"Podlech","year":"2008","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Thomas, S., Klobuch, S., Podlech, J., Plachter, B., Hoffmann, P., Renzaho, A., Theobald, M., Reddehase, M.J., Herr, W., and Lemmermann, N.A. (2015). Evaluating human T-cell therapy of cytomegalovirus organ disease in HLA-transgenic mice. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005049"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1084\/jem.20040613","article-title":"Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers","volume":"202","author":"Cobbold","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0580-9517(10)37016-4","article-title":"CD8 T-cell immunotherapy of cytomegalovirus disease in the murine model","volume":"Volume 37","author":"Kabelitz","year":"2010","journal-title":"Methods in Microbiology: Immunology of Infection"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"694588","DOI":"10.3389\/fimmu.2021.694588","article-title":"Therapeutic vaccination of hematopoietic cell transplantation recipients improves protective CD8 T-cell immunotherapy of cytomegalovirus infection","volume":"12","author":"Gergely","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Lemmermann, N.A., Krmpotic, A., Podlech, J., Brizic, I., Prager, A., Adler, H., Karbach, A., Wu, Y., Jonjic, S., and Reddehase, M.J. (2015). Non-redundant and redundant roles of cytomegalovirus gH\/gL complexes in host organ entry and intra-tissue spread. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004640"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s00430-015-0405-2","article-title":"Principles for studying in vivo attenuation of virus mutants: Defining the role of the cytomegalovirus gH\/gL\/gO complex as a paradigm","volume":"204","author":"Podlech","year":"2015","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Holtappels, R., Freitag, K., Renzaho, A., Becker, S., Lemmermann, N.A.W., and Reddehase, M.J. (2020). Revisiting CD8 T-cell \u2018memory inflation\u2019: New insights with implications for cytomegaloviruses as vaccine vectors. Vaccines, 8.","DOI":"10.3390\/vaccines8030402"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nri.2016.38","article-title":"T cell responses to cytomegalovirus","volume":"16","author":"Klenerman","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s00430-019-00587-9","article-title":"Fuel and brake of memory T cell inflation","volume":"208","author":"Welten","year":"2019","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00430-019-00607-8","article-title":"Cytomegalovirus memory inflation and immune protection","volume":"208","year":"2019","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3760","DOI":"10.4049\/jimmunol.176.6.3760","article-title":"Genome-wide analysis reveals a highly diverse CD8 T cell response to murine cytomegalovirus","volume":"176","author":"Munks","year":"2006","journal-title":"J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1099\/vir.0.031815-0","article-title":"Antigen-presenting cells of haematopoietic origin prime cytomegalovirus-specific CD8 T-cells but are not sufficient for driving memory inflation during viral latency","volume":"92","author":"Seckert","year":"2011","journal-title":"J. Gen. Virol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1128\/JVI.76.1.151-164.2002","article-title":"Two antigenic peptides from genes m123 and m164 of murine cytomegalovirus quantitatively dominate CD8 T-cell memory in the H-2d haplotype","volume":"76","author":"Holtappels","year":"2002","journal-title":"J. Virol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1099\/vir.0.012245-0","article-title":"Synergism between the components of the bipartite major immediate-early transcriptional enhancer of murine cytomegalovirus does not accelerate virus replication in cell culture and host tissues","volume":"90","author":"Kropp","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1182\/blood-2013-12-547349","article-title":"Lowest numbers of primary CD8(+) T cells can reconstitute protective immunity upon adoptive immunotherapy","volume":"124","author":"Stemberger","year":"2014","journal-title":"Blood"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.immuni.2014.05.018","article-title":"Serial transfer of single-cell-derived immunocompetence reveals stemness of CD8(+) central memory T cells","volume":"41","author":"Graef","year":"2014","journal-title":"Immunity"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0014-5793(87)80865-7","article-title":"Cyclin (PCNA, auxiliary protein of DNA polymerase delta) is a central component of the pathway(s) leading to DNA replication and cell division","volume":"220","author":"Celis","year":"1987","journal-title":"FEBS Lett."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/0022-1759(88)90441-3","article-title":"Monoclonal antibodies to proliferating cell nuclear antigen (PCNA)\/cyclin as probes for proliferating cells by immunofluorescence microscopy and flow cytometry","volume":"109","author":"Kurki","year":"1988","journal-title":"J. Immunol. Methods"},{"key":"ref_94","first-page":"e174","article-title":"Comparison of the value of PCNA and Ki-67 as markers of cell proliferation in ameloblastic tumors","volume":"18","year":"2013","journal-title":"Med. Oral Patol. Oral Y Cir. Buccal"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/path.1711620403","article-title":"Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: An index of cell proliferation with evidence of deregulated expression in some neoplasms","volume":"162","author":"Hall","year":"1990","journal-title":"J. Path."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/(SICI)1096-9896(199803)184:3<279::AID-PATH7>3.0.CO;2-4","article-title":"Induction of proliferating cell nuclear antigen and Ki-67 expression by cytomegalovirus infection","volume":"184","author":"Mate","year":"1998","journal-title":"J. Pathol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/6\/1145\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:18:44Z","timestamp":1760138324000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/6\/1145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,25]]},"references-count":96,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["v14061145"],"URL":"https:\/\/doi.org\/10.3390\/v14061145","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2022,5,25]]}}}