Memory CD4 + T cells that co-express PD1 and CTLA4 have reduced response to activating stimuli facilitating HIV latency.

Autor:	Rasmussen TA; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St., Melbourne, VIC 3000, Australia; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark., Zerbato JM; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St., Melbourne, VIC 3000, Australia., Rhodes A; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St., Melbourne, VIC 3000, Australia., Tumpach C; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St., Melbourne, VIC 3000, Australia., Dantanarayana A; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St., Melbourne, VIC 3000, Australia., McMahon JH; Department of Infectious Diseases, Alfred Hospital, Melbourne, VIC, Australia; Department of Infectious Diseases, Monash Medical Centre, Melbourne, VIC, Australia., Lau JSY; Department of Infectious Diseases, Alfred Hospital, Melbourne, VIC, Australia; Department of Infectious Diseases, Monash Medical Centre, Melbourne, VIC, Australia; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Chang JJ; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St., Melbourne, VIC 3000, Australia., Gubser C; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St., Melbourne, VIC 3000, Australia., Brown W; Monash University Department of Surgery, Alfred Health, Melbourne, VIC, Australia., Hoh R; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Krone M; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA., Pascoe R; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St., Melbourne, VIC 3000, Australia., Chiu CY; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St., Melbourne, VIC 3000, Australia., Bramhall M; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Lee HJ; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Haque A; Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Fromentin R; Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montréal, QC, Canada., Chomont N; Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montréal, QC, Canada., Milush J; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Van der Sluis RM; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St., Melbourne, VIC 3000, Australia; Aarhus Institute of Advanced Studies and Department of Biomedicine, Aarhus University, Aarhus, Denmark., Palmer S; Centre for Virus Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia., Deeks SG; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Cameron PU; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St., Melbourne, VIC 3000, Australia., Evans V; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St., Melbourne, VIC 3000, Australia; School of Medicine and Dentistry, Griffith University, Sunshine Coast, QLD, Australia., Lewin SR; Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth St., Melbourne, VIC 3000, Australia; Department of Infectious Diseases, Alfred Hospital, Melbourne, VIC, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital at The Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia. Electronic address: sharon.lewin@unimelb.edu.au.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2022 Oct 18; Vol. 3 (10), pp. 100766. Date of Electronic Publication: 2022 Oct 04.
DOI:	10.1016/j.xcrm.2022.100766
Abstrakt:	Programmed cell death 1 (PD1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4) suppress CD4 + T cell activation and may promote latent HIV infection. By performing leukapheresis (n = 21) and lymph node biopsies (n = 8) in people with HIV on antiretroviral therapy (ART) and sorting memory CD4 + T cells into subsets based on PD1/CTLA4 expression, we investigate the role of PD1 and CTLA 4 in HIV persistence. We show that double-positive (PD1 + CTLA4 + ) cells in blood contain more HIV DNA compared with double-negative (PD1 - CTLA4 - ) cells but still have a lower proportion of cells producing multiply spliced HIV RNA after stimulation as well as reduced upregulation of T cell activation and proliferation markers. Transcriptomics analyses identify differential expression of key genes regulating T cell activation and proliferation with MAF, KLRB1, and TIGIT being upregulated in double-positive compared with double-negative cells, whereas FOS is downregulated. We conclude that, in addition to being enriched for HIV DNA, double-positive cells are characterized by negative signaling and a reduced capacity to respond to stimulation, favoring HIV latency. Competing Interests: Declaration of interests S.R.L. has received funding from the National Health and Medical Research Council of Australia (NHMRC), National Institutes of Health (NIH), amfAR, Gilead Sciences, Merck, and ViiV outside of the submitted work. S.R.L. is a paid member of advisory boards to Merck, Gilead, Immunocore, Esfam, and Vaxxinity. S.R.L. has consulted for Abbvie and BMS. T.A.R. has received funding from the Danish Research Council, Region Midt Denmark, The Australian Centre for HIV and Hepatitis Research, the Melbourne HIV Cure Consortium, Gilead, and the Novo Nordisk Foundation outside of the submitted work. S.G.D. receives grant support from Gilead, Merck, and ViiV; is a member of the scientific advisory boards for BryoLogyx and Enochian Biosciences; and has consulted for AbbVie, Biotron, and Eli Lilly. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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