Identification and characterization of HIV-specific resident memory CD8 + T cells in human lymphoid tissue

• DOI: 10.1126/sciimmunol.aar4526
• Publication Date: 2018-06-01T18:15:26Z
• Authors: Marcus Buggert; Son Nguyen; Gonzalo Salgado-M...; Bertram Bengsch; Samuel Darko; Amy Ransier; Emily R. Roberts; Daniel del Alcazar; Irene Bukh Brody; Laura A. Vella; Lalit Beura; Sathi Wijeyesinghe; Ramin S. Herati; Perla M. Del Rio ...; Yuria Ablanedo-Te...; Leticia Kuri-Cerv...; Alberto Sada Japp; Sasikanth Manne; Josephine R. Giles; Shant Vartanian; Austin Huffman; Johan K. Sandberg; Emma Gostick; Gregory Nadolski; Guido Silvestri; David H. Canaday; David A. Price; Constantinos Petr...; Laura F. Su; Golnaz Vahedi; Yoav Dori; Ian Frank; Maxim G. Itkin; E. John Wherry; Steven G. Deeks; Ali Naji; Gustavo Reyes-Terán; David Masopust; Daniel C. Douek; Michael R. Betts
• Keywords: Adult; Male; 0301 basic medicine; Lymphoid Tissue; Immunology; Clinical sciences; HIV Infections; CD8-Positive T-Lymphocytes; Inbred C57BL; Virus Replication; Vaccine Related; Mice; Young Adult; 03 medical and health sciences; Genetics; 2.1 Biological and endogenous factors; Animals; Humans; Aetiology; Vaccine Related (AIDS); Biomedical and Clinical Sciences; Sequence Analysis, RNA; Prevention; Middle Aged; Viral Load; Macaca mulatta; 3. Good health; Mice, Inbred C57BL; Infectious Diseases; Good Health and Well Being; Medical Microbiology; Antirheumatic Agents; HIV-1; Sexually Transmitted Infections; HIV/AIDS; RNA; Immunization; Female; Single-Cell Analysis; Infection; Sequence Analysis; Immunologic Memory

Current paradigms of CD8 + T cell–mediated protection in HIV infection center almost exclusively on studies peripheral blood, which is thought to provide a window into immune activity at the predominant sites viral replication lymphoid tissues (LTs). Through extensive comparison thoracic duct lymph (TDL), and LTs different species, we show that many LT memory cells bear phenotypic, transcriptional, epigenetic signatures resident (T RMs ). Unlike their circulating counterparts blood or TDL, most total follicular HIV-specific also resemble . Moreover, high frequencies with skewed clonotypic profiles relative matched samples are present individuals who spontaneously control absence antiretroviral therapy (elite controllers). Single-cell RNA sequencing analysis confirmed enriched for effector-related genes compared non-T elite controllers. Together, these data indicate previous have largely failed capture major component cell responses within LTs.