{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T20:56:13Z","timestamp":1793134573275,"version":"4.5.0"},"reference-count":91,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Lymphoid tissues are an important HIV reservoir site that persists in the face of antiretroviral therapy and natural immunity. Targeting these reservoirs by harnessing the antiviral activity of local tissue-resident memory (T\n                    <jats:sub>RM<\/jats:sub>\n                    ) CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells is of great interest, but limited data exist on T\n                    <jats:sub>RM<\/jats:sub>\n                    -like cells within lymph nodes of people living with HIV (PLWH). Here, we studied tonsil CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells obtained from PLWH and uninfected controls from South Africa. We show that these cells are preferentially located outside the germinal centers (GCs), the main reservoir site for HIV, and display a low cytolytic and a transcriptionally T\n                    <jats:sub>RM<\/jats:sub>\n                    -like profile distinct from blood CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells. In PLWH, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\n                    <jats:sub>RM<\/jats:sub>\n                    -like cells are expanded and adopt a more cytolytic, activated, and exhausted phenotype not reversed by antiretroviral therapy (ART). This phenotype was enhanced in HIV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells from tonsils compared to matched blood suggesting a higher antigen burden in tonsils. Single-cell transcriptional and clonotype resolution showed that these HIV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells in the tonsils express heterogeneous signatures of T-cell activation, clonal expansion, and exhaustion ex-vivo. Interestingly, this signature was absent in a natural HIV controller, who expressed lower PD-1 and CXCR5 levels and reduced transcriptional evidence of T-cell activation, exhaustion, and cytolytic activity. These data provide important insights into lymphoid tissue-derived HIV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\n                    <jats:sub>RM<\/jats:sub>\n                    -like phenotypes in settings of HIV remission and highlight their potential for immunotherapy and targeting of the HIV reservoirs.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.912038","type":"journal-article","created":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T04:56:31Z","timestamp":1666068991000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["HIV specific CD8+ TRM-like cells in tonsils express exhaustive signatures in the absence of natural HIV control"],"prefix":"10.3389","volume":"13","author":[{"given":"Rabiah","family":"Fardoos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah K.","family":"Nyquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osaretin E.","family":"Asowata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel W.","family":"Kazer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alveera","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Ngoepe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Giandhari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ntombifuthi","family":"Mthabela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirhona","family":"Ramjit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samita","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farina","family":"Karim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren","family":"Buus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Zachary","family":"Porterfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andile L.","family":"Sibiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rishan","family":"Bipath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumeshan","family":"Moodley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren","family":"Kuhn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Son","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tulio","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thumbi","family":"Ndung\u2019u","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Goulder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex K.","family":"Shalek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alasdair","family":"Leslie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik N.","family":"Kl\u00f8verpris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1027-4","article-title":"HIV-1 remission following CCR5\u039432\/\u039432 haematopoietic stem-cell transplantation","volume":"568","author":"Gupta","year":"2019","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0802905","article-title":"Long-term control of HIV by CCR5 Delta32\/Delta32 stem-cell transplantation","volume":"360","author":"Hutter","year":"2009","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"5613","DOI":"10.4049\/jimmunol.1401161","article-title":"Compartmentalization of simian immunodeficiency virus replication within secondary lymphoid tissues of rhesus macaques is linked to disease stage and inversely related to localization of virus-specific CTL","volume":"193","author":"Connick","year":"2014","journal-title":"J Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3781","article-title":"B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers","volume":"21","author":"Fukazawa","year":"2015","journal-title":"Nat Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1056\/NEJMc1110588","article-title":"Prevention of HIV-1 infection with early antiretroviral therapy","volume":"365","author":"Cohen","year":"2011","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3283324283","article-title":"The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals","volume":"24","author":"Ray","year":"2010","journal-title":"Aids"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4113","article-title":"PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals","volume":"22","author":"Banga","year":"2016","journal-title":"Nat Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121932","article-title":"Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production","volume":"210","author":"Perreau","year":"2013","journal-title":"J Exp Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4411","article-title":"Defining total-body AIDS-virus burden with implications for curative strategies","volume":"23","author":"Estes","year":"2017","journal-title":"Nat Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0026-6","article-title":"Rapid HIV RNA rebound after antiretroviral treatment interruption in persons durably suppressed in fiebig I acute HIV infection","volume":"24","author":"Colby","year":"2018","journal-title":"Nat Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nature13594","article-title":"Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys","volume":"512","author":"Whitney","year":"2014","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3152","article-title":"HIV Reservoirs as obstacles and opportunities for an HIV cure","volume":"16","author":"Chun","year":"2015","journal-title":"Nat Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1146\/annurev-immunol-042617-053028","article-title":"Evolution of alternative adaptive immune systems in vertebrates","volume":"36","author":"Boehm","year":"2018","journal-title":"Annu Rev Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2744","article-title":"The developmental pathway for CD103(+)CD8+ tissue-resident memory T cells of skin","volume":"14","author":"Mackay","year":"2013","journal-title":"Nat Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402256","article-title":"Cutting edge: CD69 interference with sphingosine-1-phosphate receptor function regulates peripheral T cell retention","volume":"194","author":"Mackay","year":"2015","journal-title":"J Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/372190a0","article-title":"Adhesion between epithelial cells and T lymphocytes mediated by e-cadherin and the alpha e beta 7 integrin","volume":"372","author":"Cepek","year":"1994","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.08.078","article-title":"Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites","volume":"20","author":"Kumar","year":"2017","journal-title":"Cell Rep"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.09.020","article-title":"Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets","volume":"38","author":"Sathaliyawala","year":"2013","journal-title":"Immunity"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400003","article-title":"Cutting edge: resident memory CD8 T cells occupy frontline niches in secondary lymphoid organs","volume":"192","author":"Schenkel","year":"2014","journal-title":"J Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/nri.2015.3","article-title":"Tissue-resident memory T cells: local specialists in immune defence","volume":"16","author":"Mueller","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0274-9","article-title":"CD8+ T cells in HIV control, cure and prevention","author":"Collins","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3161","article-title":"Success and failure of the cellular immune response against HIV-1","volume":"16","author":"Migueles","year":"2015","journal-title":"Nat Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5403.857","article-title":"Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes","volume":"283","author":"Schmitz","year":"1999","journal-title":"Science"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.08.018","article-title":"CD8(+) lymphocytes are required for maintaining viral suppression in SIV-infected macaques treated with short-term antiretroviral therapy","volume":"45","author":"Cartwright","year":"2016","journal-title":"Immunity"},{"key":"B25","doi-asserted-by":"publisher","first-page":"8677","DOI":"10.1128\/JVI.00869-15","article-title":"Differential impact of in vivo CD8+ T lymphocyte depletion in controller versus progressor simian immunodeficiency virus-infected macaques","volume":"89","author":"Chowdhury","year":"2015","journal-title":"J Virol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000290","article-title":"Animal models to achieve an HIV cure","volume":"11","author":"Kumar","year":"2016","journal-title":"Curr Opin HIV AIDS"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.6.991","article-title":"Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques","volume":"189","author":"Jin","year":"1999","journal-title":"J Exp Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.09.006","article-title":"Molecular signature of CD8+ T cell exhaustion during chronic viral infection","volume":"27","author":"Wherry","year":"2007","journal-title":"Immunity"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.8.4911-4927.2003","article-title":"Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment","volume":"77","author":"Wherry","year":"2003","journal-title":"J Virol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00310","article-title":"Inhibitory receptors beyond T cell exhaustion","volume":"6","author":"Fuertes Marraco","year":"2015","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"e1004251","DOI":"10.1371\/journal.ppat.1004251","article-title":"T-Bet and eomes are differentially linked to the exhausted phenotype of CD8+ T cells in HIV infection","volume":"10","author":"Buggert","year":"2014","journal-title":"PloS Pathog"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nature05115","article-title":"PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression","volume":"443","author":"Day","year":"2006","journal-title":"Nature"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.7.3660","article-title":"Dynamics of T cell responses in HIV infection","volume":"168","author":"Appay","year":"2002","journal-title":"J Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/35065118","article-title":"Skewed maturation of memory HIV-specific CD8 T lymphocytes","volume":"410","author":"Champagne","year":"2001","journal-title":"Nature"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005661","article-title":"Exhaustion of activated CD8 T cells predicts disease progression in primary HIV-1 infection","volume":"12","author":"Hoffmann","year":"2016","journal-title":"PloS Pathog"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020020","article-title":"Immune activation and CD8+ T-cell differentiation towards senescence in HIV-1 infection","volume":"2","author":"Papagno","year":"2004","journal-title":"PloS Biol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0050100","article-title":"Antigen load and viral sequence diversification determine the functional profile of HIV-1-specific CD8+ T cells","volume":"5","author":"Streeck","year":"2008","journal-title":"PloS Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000362","article-title":"Programmed death-1 expression on HIV-1-specific CD8+ T cells is shaped by epitope specificity, T-cell receptor clonotype usage and antigen load","volume":"28","author":"Kl\u00f8verpris","year":"2014","journal-title":"Aids"},{"key":"B39","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.aar4526","article-title":"Identification and characterization of HIV-specific resident memory CD8(+) T cells in human lymphoid tissue","volume":"3","author":"Buggert","year":"2018","journal-title":"Sci Immunol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"6975","DOI":"10.4049\/jimmunol.178.11.6975","article-title":"CTL fail to accumulate at sites of HIV-1 replication in lymphoid tissue","volume":"178","author":"Connick","year":"2007","journal-title":"J Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007311","article-title":"Low levels of SIV-specific CD8+ T cells in germinal centers characterizes acute SIV infection","volume":"15","author":"Li","year":"2019","journal-title":"PloS Pathog"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02362","article-title":"Does b cell follicle exclusion of CD8+ T cells make lymph nodes sanctuaries of HIV replication","volume":"10","author":"Beck","year":"2019","journal-title":"Front Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.11.075","article-title":"HIV-Specific CD8(+) T cells exhibit reduced and differentially regulated cytolytic activity in lymphoid tissue","volume":"21","author":"Reuter","year":"2017","journal-title":"Cell Rep"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aax4077","article-title":"Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8(+) T cells","volume":"11","author":"Nguyen","year":"2019","journal-title":"Sci Transl Med"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2017.96","article-title":"Detection of HIV-1-specific gastrointestinal tissue resident CD8(+) T-cells in chronic infection","volume":"11","author":"Kiniry","year":"2018","journal-title":"Mucosal Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s004290100210","article-title":"Morphology and immunology of the human palatine tonsil","volume":"204","author":"Nave","year":"2001","journal-title":"Anat Embryol (Berl)"},{"key":"B47","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1016\/j.immuni.2020.09.015","article-title":"Second-strand synthesis-based massively parallel scRNA-seq reveals cellular states and molecular features of human inflammatory skin pathologies","volume":"53","author":"Hughes","year":"2020","journal-title":"Immunity"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4179","article-title":"Seq-well: portable, low-cost RNA sequencing of single cells at high throughput","volume":"14","author":"Gierahn","year":"2017","journal-title":"Nat Methods"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with harmony","volume":"16","author":"Korsunsky","year":"2019","journal-title":"Nat Methods"},{"key":"B50","doi-asserted-by":"crossref","DOI":"10.1002\/0471142727.mb0422s107","article-title":"Preparation of single-cell RNA-seq libraries for next generation sequencing","volume":"107","author":"Trombetta","year":"2014","journal-title":"Curr Protoc Mol Biol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.006","article-title":"Full-length RNA-seq from single cells using smart-seq2","volume":"9","author":"Picelli","year":"2014","journal-title":"Nat Protoc"},{"key":"B52","doi-asserted-by":"publisher","first-page":"R36","DOI":"10.1186\/gb-2013-14-4-r36","article-title":"TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions","volume":"14","author":"Kim","year":"2013","journal-title":"Genome Biol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: accurate transcript quantification from RNA-seq data with or without a reference genome","volume":"12","author":"Li","year":"2011","journal-title":"BMC Bioinf"},{"key":"B54","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13059-017-1382-0","article-title":"SCANPY: large-scale single-cell gene expression data analysis","volume":"19","author":"Wolf","year":"2018","journal-title":"Genome Biol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: A 2D graphics environment","volume":"9","author":"Hunter","year":"2007","journal-title":"Computing Sci Eng"},{"key":"B56","volume-title":"Mwaskom\/seaborn: v0.8.1","author":"Waskom.","year":"2017"},{"key":"B57","article-title":"Scikit-learn: Machine learning in python","volume":"12","author":"Pedregosa","year":"2011","journal-title":"J Mach Learn Res"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3364","article-title":"MiXCR: software for comprehensive adaptive immunity profiling","volume":"12","author":"Bolotin","year":"2015","journal-title":"Nat Methods"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa611","article-title":"Scirpy: a scanpy extension for analyzing single-cell T-cell receptor-sequencing data","volume":"36","author":"Sturm","year":"2020","journal-title":"Bioinformatics"},{"key":"B60","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1016\/j.cell.2020.11.019","article-title":"The identity of human tissue-emigrant CD8(+) T cells","volume":"183","author":"Buggert","year":"2020","journal-title":"Cell"},{"key":"B61","doi-asserted-by":"publisher","first-page":"4706","DOI":"10.1038\/s41467-019-12464-3","article-title":"Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease","volume":"10","author":"Szabo","year":"2019","journal-title":"Nat Commun"},{"key":"B62","doi-asserted-by":"publisher","first-page":"6686","DOI":"10.1073\/pnas.1913940117","article-title":"CD29 identifies IFN-\u03b3\u2013producing human CD8+ T cells with an increased cytotoxic potential","volume":"117","author":"Nicolet","year":"2020","journal-title":"Proc Natl Acad Sci"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061496","article-title":"PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection","volume":"203","author":"Petrovas","year":"2006","journal-title":"J Exp Med"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1004234","article-title":"Dominant clonotypes within HIV-specific T cell responses are programmed death-1high and CD127low and display reduced variant cross-reactivity","volume":"186","author":"Conrad","year":"2011","journal-title":"J Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-09-044826","article-title":"PD-1 up-regulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors but not in long-term nonprogressors","volume":"109","author":"Zhang","year":"2007","journal-title":"Blood"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.8.5099","article-title":"Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1high germinal center-associated subpopulation","volume":"179","author":"Haynes","year":"2007","journal-title":"J Immunol"},{"key":"B67","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.immuni.2018.06.012","article-title":"PD-1 controls follicular T helper cell positioning and function","volume":"49","author":"Shi","year":"2018","journal-title":"Immunity"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3282eee548","article-title":"PD-1 expression on human CD8 T cells depends on both state of differentiation and activation status","volume":"21","author":"Sauce","year":"2007","journal-title":"Aids"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/44385","article-title":"Two subsets of memory T lymphocytes with distinct homing potentials and effector functions","volume":"401","author":"Sallusto","year":"1999","journal-title":"Nature"},{"key":"B70","doi-asserted-by":"crossref","DOI":"10.1126\/science.aad0501","article-title":"Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq","volume":"352","author":"Tirosh","year":"2016","journal-title":"Science"},{"key":"B71","doi-asserted-by":"crossref","first-page":"D325","DOI":"10.1093\/nar\/gkaa1113","article-title":"The gene ontology resource: enriching a GOld mine","volume":"49","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. the gene ontology consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat Genet"},{"key":"B73","doi-asserted-by":"publisher","first-page":"2710","DOI":"10.3390\/ijms20112710","article-title":"Dual-specificity phosphatases in immunity and infection: An update","volume":"20","author":"Lang","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B74","doi-asserted-by":"publisher","first-page":"16484","DOI":"10.1073\/pnas.1417215111","article-title":"EGR2 is critical for peripheral na\u00efve T-cell differentiation and the T-cell response to influenza","volume":"111","author":"Du","year":"2014","journal-title":"Proc Natl Acad Sci"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160553","article-title":"Egr2 and 3 control adaptive immune responses by temporally uncoupling expansion from T cell differentiation","volume":"214","author":"Miao","year":"2017","journal-title":"J Exp Med"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-11-056168","article-title":"Activation-induced expression of CD137 permits detection, isolation, and expansion of the full repertoire of CD8+ T cells responding to antigen without requiring knowledge of epitope specificities","volume":"110","author":"Wolfl","year":"2007","journal-title":"Blood"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100833","article-title":"Cutting edge: Regulator of G protein signaling-1 selectively regulates gut T cell trafficking and colitic potential","volume":"187","author":"Gibbons","year":"2011","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2745","article-title":"Transcriptional downregulation of S1pr1 is required for the establishment of resident memory CD8+ T cells","volume":"14","author":"Skon","year":"2013","journal-title":"Nat Immunol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1517\/14712590802571928","article-title":"Elite control of HIV infection: implications for vaccine design","volume":"9","author":"Baker","year":"2009","journal-title":"Expert Opin Biol Ther"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.09.005","article-title":"HIV And HLA class I: an evolving relationship","volume":"37","author":"Goulder","year":"2012","journal-title":"Immunity"},{"key":"B81","doi-asserted-by":"publisher","first-page":"101509","DOI":"10.1016\/j.isci.2020.101509","article-title":"The whole body as the system in systems immunology","volume":"23","author":"Poon","year":"2020","journal-title":"iScience"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000530","article-title":"Tissue issues: mucosal T-cell responses in HIV-1 infection","volume":"14","author":"Shacklett","year":"2019","journal-title":"Curr Opin HIV AIDS"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.03.014","article-title":"The biology of the HIV-1 latent reservoir and implications for cure strategies","volume":"27","author":"Cohn","year":"2020","journal-title":"Cell Host Microbe"},{"key":"B84","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.cell.2020.03.005","article-title":"Curing HIV: Seeking to target and clear persistent infection","volume":"181","author":"Margolis","year":"2020","journal-title":"Cell"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2020.04.003","article-title":"'Rinse and replace': Boosting T cell turnover to reduce HIV-1 reservoirs","volume":"41","author":"Grossman","year":"2020","journal-title":"Trends Immunol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1038\/nature07662","article-title":"Enhancing SIV-specific immunity in vivo by PD-1 blockade","volume":"458","author":"Velu","year":"2009","journal-title":"Nature"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.122940","article-title":"Combination anti\u2013PD-1 and antiretroviral therapy provides therapeutic benefit against SIV","volume":"3","author":"Mylvaganam","year":"2018","journal-title":"JCI Insight"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix191","article-title":"Clinical trial of the anti-PD-L1 antibody BMS-936559 in HIV-1 infected participants on suppressive antiretroviral therapy","volume":"215","author":"Gay","year":"2017","journal-title":"J Infect Dis"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2651-8","article-title":"Distinct viral reservoirs in individuals with spontaneous control of HIV-1","volume":"585","author":"Jiang","year":"2020","journal-title":"Nature"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.122940","article-title":"Combination anti-PD-1 and antiretroviral therapy provides therapeutic benefit against SIV","volume":"3","author":"Mylvaganam","year":"2018","journal-title":"JCI Insight"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abh3034","article-title":"PD-1 blockade and vaccination provide therapeutic benefit against SIV by inducing broad and functional CD8(+) T cells in lymphoid tissue","volume":"6","author":"Rahman","year":"2021","journal-title":"Sci Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.912038\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T04:56:43Z","timestamp":1666069003000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.912038\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,18]]},"references-count":91,"alternative-id":["10.3389\/fimmu.2022.912038"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.912038","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,18]]},"article-number":"912038"}}