Distinct SIV-specific CD8+ T cells in the lymph node exhibit simultaneous effector and stem-like profiles and are associated with limited SIV persistence

• Published in: Nature immunology Vol. 25; no. 7; pp. 1245 - 1256
• Main Authors: Strongin, Zachary, Raymond Marchand, Laurence, Deleage, Claire, Pampena, M. Betina, Cardenas, Maria Andrea, Beusch, Christian Michel, Hoang, Timothy N., Urban, Elizabeth A., Gourves, Mael, Nguyen, Kevin, Tharp, Gregory K., Lapp, Stacey, Rahmberg, Andrew R., Harper, Justin, del Rio Estrada, Perla M., Gonzalez-Navarro, Mauricio, Torres-Ruiz, Fernanda, Luna-Villalobos, Yara Andrea, Avila-Rios, Santiago, Reyes-Teran, Gustavo, Sekaly, Rafick, Silvestri, Guido, Kulpa, Deanna A., Saez-Cirion, Asier, Brenchley, Jason M., Bosinger, Steven E., Gordon, David Ezra, Betts, Michael R., Kissick, Haydn T., Paiardini, Mirko
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-07-2024; Nature Publishing Group
• Subjects: 631/250; 692/699/255/1901; Antiretroviral agents; Antiretroviral therapy; Biomedical and Life Sciences; Biomedicine; CD8 antigen; Cell size; Drug therapy; Effector cells; Hepatocyte nuclear factor 1; HIV; Human immunodeficiency virus; Immune system; Immunology; Infectious Diseases; Lymph nodes; Lymphatic system; Lymphocytes; Lymphocytes T; Microenvironments; Proteomics; Viremia
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/s41590-024-01875-0

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.
Paiardini and colleagues describe a subset of lymph node HIV- and SIV-specific TOX
hi
TCF1
+
CD39
+
CD8
+
T cells that coexhibit stem- and effector-like phenotypic and transcriptional profiles and associate with reduced viral burden.