1. Identification and characterization of HIV-specific resident memory CD8 + T cells in human lymphoid tissue.
- Author
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Buggert M, Nguyen S, Salgado-Montes de Oca G, Bengsch B, Darko S, Ransier A, Roberts ER, Del Alcazar D, Brody IB, Vella LA, Beura L, Wijeyesinghe S, Herati RS, Del Rio Estrada PM, Ablanedo-Terrazas Y, Kuri-Cervantes L, Sada Japp A, Manne S, Vartanian S, Huffman A, Sandberg JK, Gostick E, Nadolski G, Silvestri G, Canaday DH, Price DA, Petrovas C, Su LF, Vahedi G, Dori Y, Frank I, Itkin MG, Wherry EJ, Deeks SG, Naji A, Reyes-Terán G, Masopust D, Douek DC, and Betts MR
- Subjects
- Adult, Animals, Antirheumatic Agents pharmacology, Antirheumatic Agents therapeutic use, CD8-Positive T-Lymphocytes metabolism, Female, HIV Infections blood, HIV Infections drug therapy, HIV Infections virology, Humans, Lymphoid Tissue drug effects, Lymphoid Tissue immunology, Macaca mulatta, Male, Mice, Mice, Inbred C57BL, Middle Aged, Sequence Analysis, RNA, Single-Cell Analysis methods, Viral Load drug effects, Viral Load immunology, Virus Replication drug effects, Virus Replication immunology, Young Adult, CD8-Positive T-Lymphocytes immunology, HIV Infections immunology, HIV-1 immunology, Immunologic Memory, Lymphoid Tissue cytology
- Abstract
Current paradigms of CD8
+ T cell-mediated protection in HIV infection center almost exclusively on studies of peripheral blood, which is thought to provide a window into immune activity at the predominant sites of viral replication in lymphoid tissues (LTs). Through extensive comparison of blood, thoracic duct lymph (TDL), and LTs in different species, we show that many LT memory CD8+ T cells bear phenotypic, transcriptional, and epigenetic signatures of resident memory T cells (TRMs ). Unlike their circulating counterparts in blood or TDL, most of the total and follicular HIV-specific CD8+ T cells in LTs also resemble TRMs Moreover, high frequencies of HIV-specific CD8+ TRMs with skewed clonotypic profiles relative to matched blood samples are present in LTs of individuals who spontaneously control HIV replication in the absence of antiretroviral therapy (elite controllers). Single-cell RNA sequencing analysis confirmed that HIV-specific TRMs are enriched for effector-related immune genes and signatures compared with HIV-specific non-TRMs in elite controllers. Together, these data indicate that previous studies in blood have largely failed to capture the major component of HIV-specific CD8+ T cell responses resident within LTs., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)- Published
- 2018
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