دورية أكاديمية
Distinct SIV-specific CD8 + T cells in the lymph node exhibit simultaneous effector and stem-like profiles and are associated with limited SIV persistence.
| العنوان: | Distinct SIV-specific CD8 + T cells in the lymph node exhibit simultaneous effector and stem-like profiles and are associated with limited SIV persistence. |
|---|---|
| المؤلفون: | Strongin Z; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA., Raymond Marchand L; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA., Deleage C; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA., Pampena MB; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Center for AIDS Research and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Cardenas MA; Department of Urology, Emory University School of Medicine, Atlanta, GA, USA., Beusch CM; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden., Hoang TN; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA., Urban EA; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA., Gourves M; Institut Pasteur, Université Paris Cité, Viral Reservoirs and Immune Control Unit, Paris, France.; Institut Pasteur, Université Paris Cité, HIV Inflammation and Persistence Unit, Paris, France., Nguyen K; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA., Tharp GK; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA., Lapp S; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA., Rahmberg AR; Barrier Immunity Section, Laboratory of Viral Diseases, NIAIDNIH, Bethesda, MD, USA., Harper J; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA., Del Rio Estrada PM; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.; Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico., Gonzalez-Navarro M; Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico., Torres-Ruiz F; Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico., Luna-Villalobos YA; Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico., Avila-Rios S; Centro de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico., Reyes-Teran G; Comision Coordinadora de los Institutos Nacionales de Salud y Hospitales de Alta Especialidad, Mexico City, Mexico., Sekaly R; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA.; Winship Cancer Institute, Emory University, Atlanta, GA, USA., Silvestri G; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA., Kulpa DA; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA., Saez-Cirion A; Institut Pasteur, Université Paris Cité, Viral Reservoirs and Immune Control Unit, Paris, France.; Institut Pasteur, Université Paris Cité, HIV Inflammation and Persistence Unit, Paris, France., Brenchley JM; Barrier Immunity Section, Laboratory of Viral Diseases, NIAIDNIH, Bethesda, MD, USA., Bosinger SE; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA., Gordon DE; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA., Betts MR; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Center for AIDS Research and Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Kissick HT; Department of Urology, Emory University School of Medicine, Atlanta, GA, USA.; Emory Vaccine Center, Emory University, Atlanta, GA, USA.; Winship Cancer Institute, Emory University, Atlanta, GA, USA., Paiardini M; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA. mirko.paiardini@emory.edu.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA. mirko.paiardini@emory.edu.; Emory Vaccine Center, Emory University, Atlanta, GA, USA. mirko.paiardini@emory.edu. |
| المصدر: | Nature immunology [Nat Immunol] 2024 Jul; Vol. 25 (7), pp. 1245-1256. Date of Electronic Publication: 2024 Jun 17. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature America Inc Country of Publication: United States NLM ID: 100941354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2916 (Electronic) Linking ISSN: 15292908 NLM ISO Abbreviation: Nat Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Nature America Inc. c2000- |
| مواضيع طبية MeSH: | Simian Immunodeficiency Virus*/immunology , CD8-Positive T-Lymphocytes*/immunology , Simian Acquired Immunodeficiency Syndrome*/immunology , Simian Acquired Immunodeficiency Syndrome*/virology , Lymph Nodes*/immunology, Animals ; Humans ; Macaca mulatta ; HIV Infections/immunology ; HIV Infections/virology ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism |
| مستخلص: | Human immunodeficiency virus (HIV) cure efforts are increasingly focused on harnessing CD8 + T cell functions, which requires a deeper understanding of CD8 + T cells promoting HIV control. Here we identifiy an antigen-responsive TOX hi TCF1 + CD39 + CD8 + T cell population with high expression of inhibitory receptors and low expression of canonical cytolytic molecules. Transcriptional analysis of simian immunodeficiency virus (SIV)-specific CD8 + T cells and proteomic analysis of purified CD8 + T cell subsets identified TOX hi TCF1 + CD39 + CD8 + T cells as intermediate effectors that retained stem-like features with a lineage relationship with terminal effector T cells. TOX hi TCF1 + CD39 + CD8 + T cells were found at higher frequency than TCF1 - CD39 + CD8 + T cells in follicular microenvironments and were preferentially located in proximity of SIV-RNA + cells. Their frequency was associated with reduced plasma viremia and lower SIV reservoir size. Highly similar TOX hi TCF1 + CD39 + CD8 + T cells were detected in lymph nodes from antiretroviral therapy-naive and antiretroviral therapy-suppressed people living with HIV, suggesting this population of CD8 + T cells contributes to limiting SIV and HIV persistence. (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.) |
| References: | Blank, C. U. et al. Defining ‘T cell exhaustion’. Nat. Rev. Immunol. 19, 665–674 (2019). (PMID: 315708797286441) Alfei, F. et al. TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection. Nature 571, 265–269 (2019). (PMID: 31207605) Scott, A. C. et al. TOX is a critical regulator of tumour-specific T cell differentiation. Nature 571, 270–274 (2019). (PMID: 312076047698992) Khan, O. et al. TOX transcriptionally and epigenetically programs CD8 + T cell exhaustion. Nature 571, 211–218 (2019). (PMID: 312076036713202) Yao, C. et al. Single-cell RNA-seq reveals TOX as a key regulator of CD8 + T cell persistence in chronic infection. Nat. Immunol. 20, 890–901 (2019). (PMID: 312094006588409) Seo, H. et al. TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8 + T cell exhaustion. Proc. Natl Acad. Sci. USA 116, 12410–12415 (2019). (PMID: 311521406589758) Beltra, J. C. et al. Developmental relationships of four exhausted CD8 + T cell subsets reveals underlying transcriptional and epigenetic landscape control mechanisms. Immunity 52, 825–841 (2020). (PMID: 323968478360766) Sekine, T. et al. TOX is expressed by exhausted and polyfunctional human effector memory CD8 + T cells. Sci. Immunol. 5, eaba7918 (2020). (PMID: 32620560) Heim, K. et al. TOX defines the degree of CD8 + T cell dysfunction in distinct phases of chronic HBV infection. Gut 70, 1550–1560 (2020). (PMID: 33097558) Im, S. J. et al. Defining CD8 + T cells that provide the proliferative burst after PD-1 therapy. Nature 537, 417–421 (2016). (PMID: 275012485297183) Hudson, W. H. et al. Proliferating transitory T cells with an effector-like transcriptional signature emerge from PD-1 + stem-like CD8 + T cells during chronic infection. Immunity 51, 1043–1058 (2019). (PMID: 318108826920571) Collins, D. R., Gaiha, G. D. & Walker, B. D. CD8 + T cells in HIV control, cure and prevention. Nat. Rev. Immunol. 20, 471–482 (2020). (PMID: 320515407222980) Day, C. L. et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443, 350–354 (2006). (PMID: 16921384) Trautmann, L. et al. Upregulation of PD-1 expression on HIV-specific CD8 + T cells leads to reversible immune dysfunction. Nat. Med. 12, 1198–1202 (2006). (PMID: 16917489) Petrovas, C. et al. PD-1 is a regulator of virus-specific CD8 + T cell survival in HIV infection. J. Exp. Med. 203, 2281–2292 (2006). (PMID: 169543722118095) Hoffmann, M. et al. Exhaustion of activated CD8 T cells predicts disease progression in primary HIV-1 infection. PLoS Pathog. 12, e1005661 (2016). (PMID: 274158284945085) Chew, G. M. et al. TIGIT marks exhausted T cells, correlates with disease progression, and serves as a target for immune restoration in HIV and SIV infection. PLoS Pathog. 12, e1005349 (2016). (PMID: 267414904704737) Collins, D. R. et al. Functional impairment of HIV-specific CD8 + T cells precedes aborted spontaneous control of viremia. Immunity 54, 2372–2384 (2021). (PMID: 344962238516715) Bengsch, B. et al. Epigenomic-guided mass cytometry profiling reveals disease-specific features of exhausted CD8 T cells. Immunity 48, 1029–1045 (2018). (PMID: 297681646010198) Reuter, M. A. et al. HIV-specific CD8 + T cells exhibit reduced and differentially regulated cytolytic activity in lymphoid tissue. Cell Rep. 21, 3458–3470 (2017). (PMID: 292623265764192) Nguyen, S. et al. Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8 + T cells. Sci. Transl. Med. 11, eaax4077 (2019). (PMID: 318527987265335) Buggert, M. et al. Identification and characterization of HIV-specific resident memory CD8 + T cells in human lymphoid tissue. Sci. Immunol. 3, eaar4526 (2018). (PMID: 298582866357781) Collins, D. R. et al. Cytolytic CD8 + T cells infiltrate germinal centers to limit ongoing HIV replication in spontaneous controller lymph nodes. Sci. Immunol. 8, eade5872 (2023). (PMID: 3720576710231436) Ward, A. R., Mota, T. M. & Jones, R. B. Immunological approaches to HIV cure. Semin. Immunol. 51, 101412 (2021). (PMID: 32981836) Deeks, S. G. et al. Research priorities for an HIV cure: International AIDS Society Global Scientific Strategy 2021. Nat. Med. 27, 2085–2098 (2021). (PMID: 34848888) Huang, S. et al. Increased TOX expression concurrent with PD-1, Tim-3, and CD244 in T cells from patients with non-Hodgkin lymphoma. Asia Pac. J. Clin. Oncol. 18, 143–149 (2022). (PMID: 33608984) Wang, X. et al. TOX promotes the exhaustion of antitumor CD8 + T cells by preventing PD1 degradation in hepatocellular carcinoma. J. Hepatol. 71, 731–741 (2019). (PMID: 31173813) Gupta, P. K. et al. CD39 expression identifies terminally exhausted CD8 + T cells. PLoS Pathog. 11, e1005177 (2015). (PMID: 264855194618999) Sade-Feldman, M. et al. Defining T cell states associated with response to checkpoint immunotherapy in melanoma. Cell 175, 998–1013 (2018). (PMID: 303884566641984) Canale, F. P. et al. CD39 expression defines cell exhaustion in tumor-infiltrating CD8 + T cells. Cancer Res. 78, 115–128 (2018). (PMID: 29066514) Abbas, H. A. et al. Single cell T cell landscape and T cell receptor repertoire profiling of AML in context of PD-1 blockade therapy. Nat. Commun. 12, 6071 (2021). (PMID: 346638078524723) Jonsson, A. H. et al. Granzyme K + CD8 T cells form a core population in inflamed human tissue. Sci. Transl. Med. 14, eabo0686 (2022). (PMID: 357045999972878) Arbones, M. L. et al. Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. Immunity 1, 247–260 (1994). (PMID: 7534203) Takeuchi, A. et al. CRTAM confers late-stage activation of CD8 + T cells to regulate retention within lymph node. J. Immunol. 183, 4220–4228 (2009). (PMID: 19752223) Guma, M. et al. The CD94/NKG2C killer lectin-like receptor constitutes an alternative activation pathway for a subset of CD8 + T cells. Eur. J. Immunol. 35, 2071–2080 (2005). (PMID: 15940674) Trkola, A. et al. Genetic subtype-independent inhibition of human immunodeficiency virus type 1 replication by CC and CXC chemokines. J. Virol. 72, 396–404 (1998). (PMID: 9420238109387) Cocchi, F. et al. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science 270, 1811–1815 (1995). (PMID: 8525373) Ichii, H. et al. Role for Bcl-6 in the generation and maintenance of memory CD8 + T cells. Nat. Immunol. 3, 558–563 (2002). (PMID: 12021781) Sun, Q. et al. BCL6 promotes a stem-like CD8 + T cell program in cancer via antagonizing BLIMP1. Sci. Immunol. 8, eadh1306 (2023). (PMID: 37862431) Eberhardt, C. S. et al. Functional HPV-specific PD-1 + stem-like CD8 T cells in head and neck cancer. Nature 597, 279–284 (2021). (PMID: 3447128510201342) Sekaly, R. et al. Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption. Preprint at Res. Sq. https://doi.org/10.21203/rs.3.rs-3175716/v1 (2023). Petrovas, C. et al. Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies. Sci. Transl. Med. 9, eaag2285 (2017). (PMID: 281008335497679) Yates, K. B. et al. Epigenetic scars of CD8 + T cell exhaustion persist after cure of chronic infection in humans. Nat. Immunol. 22, 1020–1029 (2021). (PMID: 343125478600539) Bruner, K. M. et al. A quantitative approach for measuring the reservoir of latent HIV-1 proviruses. Nature 566, 120–125 (2019). (PMID: 307009136447073) Utzschneider, D. T. et al. T cell factor 1-expressing memory-like CD8(+) T cells sustain the immune response to chronic viral infections. Immunity 45, 415–427 (2016). (PMID: 27533016) Kiniry, B. E. et al. Differential expression of CD8 + T cell cytotoxic effector molecules in blood and gastrointestinal mucosa in HIV-1 infection. J. Immunol. 200, 1876–1888 (2018). (PMID: 29352005) Passaes, C. et al. Optimal maturation of the SIV-specific CD8 + T cell response after primary infection is associated with natural control of SIV: ANRS SIC study. Cell Rep. 32, 108174 (2020). (PMID: 32966788) Rutishauser, R. L. et al. TCF-1 regulates HIV-specific CD8 + T cell expansion capacity. JCI Insight 6, e136648 (2021). (PMID: 333517857934879) Mvaya, L. et al. Differential localization and limited cytotoxic potential of duodenal CD8 + T cells. JCI Insight 7, e154195 (2022). (PMID: 351329668855799) Fardoos, R. et al. HIV specific CD8 + TRM-like cells in tonsils express exhaustive signatures in the absence of natural HIV control. Front. Immunol. 13, 912038 (2022). (PMID: 363305319623418) McGary, C. S. et al. CTLA-4 + PD-1− memory CD4 + T cells critically contribute to viral persistence in antiretroviral therapy-suppressed, SIV-infected rhesus macaques. Immunity 47, 776–788 (2017). (PMID: 290459065679306) Li, H. et al. Envelope residue 375 substitutions in simian-human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques. Proc. Natl Acad. Sci. USA 113, E3413–E3422 (2016). (PMID: 272474004914158) Langner, C. A. & Brenchley, J. M. FRugally optimized DNA cctomer (FRODO) qPCR measurement of HIV and SIV in human and nonhuman primate samples. Curr. Protoc. 1, e93 (2021). (PMID: 338615008054980) Strongin, Z. et al. The role of CD101-expressing CD4 T cells in HIV/SIV pathogenesis and persistence. PLoS Pathog. 18, e1010723 (2022). (PMID: 358677229348691) Hoang, T. N. et al. Baricitinib treatment resolves lower-airway macrophage inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques. Cell 184, 460–475 (2021). (PMID: 33278358) Satija, R., Farrell, J. A., Gennert, D., Schier, A. F. & Regev, A. Spatial reconstruction of single-cell gene expression data. Nat. Biotechnol. 33, 495–502 (2015). (PMID: 258679234430369) DeTomaso, D. & Yosef, N. FastProject: a tool for low-dimensional analysis of single-cell RNA-seq data. BMC Bioinf. 17, 315 (2016). Bolotin, D. A. et al. MiXCR: software for comprehensive adaptive immunity profiling. Nat. Methods 12, 380–381 (2015). (PMID: 25924071) Black, S. et al. CODEX multiplexed tissue imaging with DNA-conjugated antibodies. Nat. Protoc. 16, 3802–3835 (2021). (PMID: 342158628647621) Deleage, C. et al. Defining HIV and SIV reservoirs in lymphoid tissues. Pathog. Immun. 1, 68–106 (2016). (PMID: 274300324943335) Bankhead, P. et al. QuPath: open source software for digital pathology image analysis. Sci. Rep. 7, 16878 (2017). (PMID: 292038795715110) Skowronek, P. et al. Rapid and in-depth coverage of the (phospho-)proteome with deep libraries and optimal window design for dia-PASEF. Mol. Cell Proteom. 21, 100279 (2022). Bruderer, R. et al. Optimization of experimental parameters in data-independent mass spectrometry significantly increases depth and reproducibility of results. Mol. Cell Proteom. 16, 2296–2309 (2017). Lazar, C., Gatto, L., Ferro, M., Bruley, C. & Burger, T. Accounting for the multiple natures of missing values in label-free quantitative proteomics data sets to compare imputation strategies. J. Proteome Res. 15, 1116–1125 (2016). (PMID: 26906401) |
| معلومات مُعتمدة: | UM1AI164562 Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID); R01AI116379 Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID); R56AI150401 Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID); 2023-00510 Vetenskapsrådet (Swedish Research Council); 75N91019D00024 United States CA NCI NIH HHS; 1ZIAAI001029 U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID); OD026799 U.S. Department of Health & Human Services | National Institutes of Health (NIH); 75N91019D00024 United States CA NCI NIH HHS |
| تواريخ الأحداث: | Date Created: 20240617 Date Completed: 20240704 Latest Revision: 20240705 |
| رمز التحديث: | 20240706 |
| DOI: | 10.1038/s41590-024-01875-0 |
| PMID: | 38886592 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1529-2916 |
|---|---|
| DOI: | 10.1038/s41590-024-01875-0 |