| Autor: |
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 |
| Zdroj: |
Nature Immunology; 20240101, Issue: Preprints p1-12, 12p |
| Abstrakt: |
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 TOXhiTCF1+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 TOXhiTCF1+CD39+CD8+T cells as intermediate effectors that retained stem-like features with a lineage relationship with terminal effector T cells. TOXhiTCF1+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 TOXhiTCF1+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. |
| Databáze: |
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