{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T05:22:04Z","timestamp":1741324924197,"version":"3.38.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>T lymphocytes play a central role in many human immunologic disorders, including autoimmune and alloimmune diseases. In hematopoietic stem cell transplantation, acute graft-versus-host-disease (GVHD) is caused by an attack on the recipient\u2019s tissues from donor allogeneic T cells. Selectively depleting GVHD-causing cells prior to transplant may prevent GVHD. In this study, we evaluated 24 chalcogenorhodamine photosensitizers for their ability to selectively deplete reactive T lymphocytes and identified the photosensitizer 2-Se-Cl, which accumulates in stimulated T cells in proportion to oxidative phosphorylation. The photosensitizer is also a potent stimulator of P-glycoprotein (P-gp). Enhanced P-gp activity promotes the efficient removal of photosensitizer not sequestered in mitochondria and protects resting lymphocytes that are essential for antipathogen and antitumor responses. To evaluate the selective depletion of alloimmune responses, donor C57BL\/6 splenocytes were cocultured for 5 d with irradiated BALB\/c splenocytes and then photodepleted (PD). PD-treated splenocytes were infused into lethally irradiated BALB\/c (same-party) or C3H\/HeJ (third-party) mice. Same-party mice that received PD-treated splenocytes at the time of transplant lived 100 d without evidence of GVHD. In contrast, all mice that received untreated primed splenocytes and third-party mice that received PD-treated splenocytes died of lethal GVHD. To evaluate the preservation of antiviral immune responses, acute lymphocytic choriomeningitis virus infection was used. After photodepletion, expansion of Ag-specific naive CD8+ T cells and viral clearance remained fully intact. The high selectivity of this novel photosensitizer may have broad applications and provide alternative treatment options for patients with T lymphocyte\u2013mediated diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1402445","type":"journal-article","created":{"date-parts":[[2016,7,26]],"date-time":"2016-07-26T02:43:28Z","timestamp":1469501008000},"page":"1631-1641","source":"Crossref","is-referenced-by-count":1,"title":["Targeting T Cell Bioenergetics by Modulating P-Glycoprotein Selectively Depletes Alloreactive T Cells To Prevent Graft-versus-Host Disease"],"prefix":"10.1093","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7570-8511","authenticated-orcid":false,"given":"Zachariah A","family":"McIver","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology, Wake Forest University School of Medicine , Winston-Salem, NC 27157"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason M","family":"Grayson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Wake Forest School of Medicine , Winston-Salem, NC 27157"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin N","family":"Coe","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Wake Forest University School of Medicine , Winston-Salem, NC 27157"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline E","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State University of New York , Buffalo, NY 14260"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory A","family":"Schamerhorn","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State University of New York , Buffalo, NY 14260"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7051-6534","authenticated-orcid":false,"given":"Tymish Y","family":"Ohulchanskyy","sequence":"additional","affiliation":[{"name":"Institute for Lasers, Photonics, and Biophotonics, Department of Chemistry, State University of New York , Buffalo, NY 14260"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle K","family":"Linder","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State University of New York , Buffalo, NY 14260"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kellie S","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State University of New York , Buffalo, NY 14260"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7368-4819","authenticated-orcid":false,"given":"Roy S","family":"Weiner","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Tulane University School of Medicine , New Orleans, LA 70112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8815-1481","authenticated-orcid":false,"given":"Michael R","family":"Detty","sequence":"additional","affiliation":[{"name":"Department of Chemistry, State University of New York , Buffalo, NY 14260"},{"name":"Institute for Lasers, Photonics, and Biophotonics, Department of Chemistry, State University of New York , Buffalo, NY 14260"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,9,1]]},"reference":[{"key":"2025030617475013700_r1","first-page":"151","article-title":"Marrow transplantation for acute nonlymphoblastic leukemia in first remission: toxicity and long-term follow-up of patients conditioned with single dose or fractionated total body irradiation","volume":"1","author":"Deeg","year":"1986","journal-title":"Bone Marrow Transplant."},{"key":"2025030617475013700_r2","first-page":"21","article-title":"The biology of graft-versus-host reactions","volume":"62","author":"Billingham","year":"1966-1967","journal-title":"Harvey Lect."},{"key":"2025030617475013700_r3","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1056\/NEJM199810223391702","article-title":"Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype","volume":"339","author":"Aversa","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"2025030617475013700_r4","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1182\/blood.V91.3.1083","article-title":"T-cell-depleted allogeneic bone marrow transplantation as postremission therapy for acute myelogenous leukemia: freedom from relapse in the absence of graft-versus-host disease","volume":"91","author":"Papadopoulos","year":"1998","journal-title":"Blood"},{"key":"2025030617475013700_r5","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1016\/j.bbmt.2006.08.034","article-title":"T cell depleted peripheral blood stem cell allotransplantation with T cell add back for patients with hematological malignancies: effect of chronic GVHD on outcome","volume":"12","author":"Montero","year":"2006","journal-title":"Biol. Blood Marrow Transplant."},{"key":"2025030617475013700_r6","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1046\/j.1365-2141.1998.00748.x","article-title":"Specific depletion of alloreactive T cells in HLA-identical siblings: a method for separating graft-versus-host and graft-versus-leukaemia reactions","volume":"101","author":"Mavroudis","year":"1998","journal-title":"Br. J. Haematol."},{"key":"2025030617475013700_r7","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/sj.bmt.1704142","article-title":"Tissue-restricted T cell alloresponses across HLA barriers: selection and identification of leukemia-restricted CTL in HLA-mismatched stimulator-responder pairs","volume":"32","author":"Fujiwara","year":"2003","journal-title":"Bone Marrow Transplant."},{"key":"2025030617475013700_r8","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1182\/blood-2005-01-0393","article-title":"Selective depletion of alloreactive donor lymphocytes: a novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation","volume":"106","author":"Solomon","year":"2005","journal-title":"Blood"},{"key":"2025030617475013700_r9","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.bbmt.2012.10.004","article-title":"Depletion of naive lymphocytes with fas ligand ex vivo prevents graft-versus-host disease without impairing T cell support of engraftment or graft-versus-tumor activity","volume":"19","author":"Askenasy","year":"2013","journal-title":"Biol. Blood Marrow Transplant."},{"key":"2025030617475013700_r10","doi-asserted-by":"crossref","first-page":"4392","DOI":"10.1182\/blood-2007-08-104471","article-title":"A clinical-scale selective allodepletion approach for the treatment of HLA-mismatched and matched donor-recipient pairs using expanded T lymphocytes as antigen-presenting cells and a TH9402-based photodepletion technique","volume":"111","author":"Mielke","year":"2008","journal-title":"Blood"},{"key":"2025030617475013700_r11","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1016\/j.bbmt.2011.05.017","article-title":"Immune reconstitution in recipients of photodepleted HLA-identical sibling donor stem cell transplantations: T cell subset frequencies predict outcome","volume":"17","author":"McIver","year":"2011","journal-title":"Biol. Blood Marrow Transplant."},{"key":"2025030617475013700_r12","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1016\/j.bbmt.2011.05.019","article-title":"Selectively T cell-depleted allografts from HLA-matched sibling donors followed by low-dose posttransplantation immunosuppression to improve transplantation outcome in patients with hematologic malignancies","volume":"17","author":"Mielke","year":"2011","journal-title":"Biol. Blood Marrow Transplant."},{"key":"2025030617475013700_r13","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","volume":"324","author":"Vander Heiden","year":"2009","journal-title":"Science"},{"key":"2025030617475013700_r14","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1096\/fasebj.11.5.9141507","article-title":"Aerobic glycolysis by proliferating cells: a protective strategy against reactive oxygen species","volume":"11","author":"Brand","year":"1997","journal-title":"FASEB J."},{"key":"2025030617475013700_r15","doi-asserted-by":"crossref","first-page":"67ra8","DOI":"10.1126\/scitranslmed.3001975","article-title":"Manipulating the bioenergetics of alloreactive T cells causes their selective apoptosis and arrests graft-versus-host disease","volume":"3","author":"Gatza","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"2025030617475013700_r16","doi-asserted-by":"crossref","first-page":"14336","DOI":"10.1073\/pnas.1221740110","article-title":"CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability","volume":"110","author":"van der Windt","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030617475013700_r17","doi-asserted-by":"crossref","first-page":"3735","DOI":"10.1073\/pnas.74.9.3735","article-title":"High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase","volume":"74","author":"Bustamante","year":"1977","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030617475013700_r18","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1084\/jem.160.2.521","article-title":"Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence","volume":"160","author":"Ahmed","year":"1984","journal-title":"J. Exp. Med."},{"key":"2025030617475013700_r19","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1182\/blood.V99.9.3083","article-title":"Prevention of graft-versus-host disease while preserving graft-versus-leukemia effect after selective depletion of host-reactive T cells by photodynamic cell purging process","volume":"99","author":"Chen","year":"2002","journal-title":"Blood"},{"key":"2025030617475013700_r20","doi-asserted-by":"crossref","first-page":"3230","DOI":"10.1182\/blood.V88.8.3230.bloodjournal8883230","article-title":"An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation: I. The roles of minor H antigens and endotoxin","volume":"88","author":"Cooke","year":"1996","journal-title":"Blood"},{"key":"2025030617475013700_r21","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1084\/jem.20070723","article-title":"Antibody to the dendritic cell surface activation antigen CD83 prevents acute graft-versus-host disease. [Published erratum appears in 2009 J. Exp. Med. 206: 1203.]","volume":"206","author":"Wilson","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025030617475013700_r22","doi-asserted-by":"crossref","first-page":"11246","DOI":"10.1128\/JVI.78.20.11246-11257.2004","article-title":"Antioxidant treatment reduces expansion and contraction of antigen-specific CD8+ T cells during primary but not secondary viral infection","volume":"78","author":"Laniewski","year":"2004","journal-title":"J. Virol."},{"key":"2025030617475013700_r23","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.4049\/jimmunol.170.9.4745","article-title":"Mitochondrial potential and reactive oxygen intermediates in antigen-specific CD8+ T cells during viral infection","volume":"170","author":"Grayson","year":"2003","journal-title":"J. Immunol."},{"key":"2025030617475013700_r24","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/978-1-60761-720-4_4","article-title":"Assessment of mitochondrial dysfunction in lymphocytes of patients with systemic lupus erythematosus","volume":"900","author":"Perl","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"2025030617475013700_r25","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1756-185X.2011.01598.x","article-title":"Glycolysis and rheumatoid arthritis","volume":"14","author":"Chang","year":"2011","journal-title":"Int. J. Rheum. Dis."},{"key":"2025030617475013700_r26","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.immuni.2011.09.021","article-title":"The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation","volume":"35","author":"Wang","year":"2011","journal-title":"Immunity"},{"key":"2025030617475013700_r27","doi-asserted-by":"crossref","first-page":"3328","DOI":"10.1021\/jm900253g","article-title":"Rhodamine inhibitors of P-glycoprotein: an amide\/thioamide \u201cswitch\u201d for ATPase activity","volume":"52","author":"Gannon II","year":"2009","journal-title":"J. Med. Chem."},{"key":"2025030617475013700_r28","doi-asserted-by":"crossref","first-page":"4290","DOI":"10.1016\/j.bmc.2012.05.075","article-title":"Thiorhodamines containing amide and thioamide functionality as inhibitors of the ATP-binding cassette drug transporter P-glycoprotein (ABCB1)","volume":"20","author":"Orchard","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"2025030617475013700_r29","doi-asserted-by":"crossref","first-page":"4636","DOI":"10.1182\/blood-2003-09-3068","article-title":"T-cell lymphoma as a model for the use of histone deacetylase inhibitors in cancer therapy: impact of depsipeptide on molecular markers, therapeutic targets, and mechanisms of resistance","volume":"103","author":"Piekarz","year":"2004","journal-title":"Blood"},{"key":"2025030617475013700_r30","doi-asserted-by":"crossref","first-page":"5188","DOI":"10.4049\/jimmunol.171.10.5188","article-title":"T cell activation-induced mitochondrial hyperpolarization is mediated by Ca2+- and redox-dependent production of nitric oxide","volume":"171","author":"Nagy","year":"2003","journal-title":"J. Immunol."},{"key":"2025030617475013700_r31","doi-asserted-by":"crossref","first-page":"3897","DOI":"10.1021\/jm040074b","article-title":"Current clinical and preclinical photosensitizers for use in photodynamic therapy","volume":"47","author":"Detty","year":"2004","journal-title":"J. Med. Chem."},{"key":"2025030617475013700_r32","doi-asserted-by":"crossref","first-page":"556","DOI":"10.3390\/toxins6020556","article-title":"Soluble T cell receptor V\u03b2 domains engineered for high-affinity binding to staphylococcal or streptococcal superantigens","volume":"6","author":"Sharma","year":"2014","journal-title":"Toxins (Basel)"},{"key":"2025030617475013700_r33","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.immuni.2009.11.010","article-title":"Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo","volume":"32","author":"Kalia","year":"2010","journal-title":"Immunity"},{"key":"2025030617475013700_r34","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1124\/jpet.114.218099","article-title":"Anaplerotic metabolism of alloreactive T cells provides a metabolic approach to treat graft-versus-host disease","volume":"351","author":"Glick","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2025030617475013700_r35","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.immuni.2011.12.007","article-title":"Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development","volume":"36","author":"van der Windt","year":"2012","journal-title":"Immunity"},{"key":"2025030617475013700_r36","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1177\/2040620713489842","article-title":"Treatment and management of graft-versus-host disease: improving response and survival","volume":"4","author":"Garnett","year":"2013","journal-title":"Ther. Adv. Hematol."},{"key":"2025030617475013700_r37","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1182\/blood.V76.8.1464.1464","article-title":"A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment","volume":"76","author":"Martin","year":"1990","journal-title":"Blood"},{"key":"2025030617475013700_r38","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1111\/j.1537-2995.2006.00842.x","article-title":"The National Marrow Donor Program with emphasis on the early years","volume":"46","author":"McCullough","year":"2006","journal-title":"Transfusion"},{"key":"2025030617475013700_r39","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1182\/blood-2005-10-4004","article-title":"Ethnicity and survival in childhood acute myeloid leukemia: a report from the Children\u2019s Oncology Group","volume":"108","author":"Aplenc","year":"2006","journal-title":"Blood"},{"key":"2025030617475013700_r40","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/j.bbmt.2008.06.005","article-title":"Paucity of HLA-identical unrelated donors for African-Americans with hematologic malignancies: the need for new donor options","volume":"14","author":"Dew","year":"2008","journal-title":"Biol. Blood Marrow Transplant."},{"key":"2025030617475013700_r41","doi-asserted-by":"crossref","first-page":"4576","DOI":"10.1182\/blood-2007-06-097386","article-title":"High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation","volume":"110","author":"Lee","year":"2007","journal-title":"Blood"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/197\/5\/1631\/61580537\/1402445.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/197\/5\/1631\/61580537\/1402445.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T19:01:12Z","timestamp":1741287672000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/197\/5\/1631\/7974597"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,1]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,9,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1402445","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"type":"print","value":"0022-1767"},{"type":"electronic","value":"1550-6606"}],"subject":[],"published-other":{"date-parts":[[2016,9]]},"published":{"date-parts":[[2016,9,1]]}}}