HIV specific CD8 + T RM -like cells in tonsils express exhaustive signatures in the absence of natural HIV control.

Autor: Fardoos R; Africa Health Research Institute (AHRI), Durban, South Africa.; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Nyquist SK; Institute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States.; Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, United States., Asowata OE; Africa Health Research Institute (AHRI), Durban, South Africa., Kazer SW; Institute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States., Singh A; Africa Health Research Institute (AHRI), Durban, South Africa., Ngoepe A; Africa Health Research Institute (AHRI), Durban, South Africa., Giandhari J; KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa., Mthabela N; Africa Health Research Institute (AHRI), Durban, South Africa., Ramjit D; Africa Health Research Institute (AHRI), Durban, South Africa., Singh S; Africa Health Research Institute (AHRI), Durban, South Africa., Karim F; Africa Health Research Institute (AHRI), Durban, South Africa., Buus S; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark., Anderson F; Discipline of General Surgery, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, Durban, South Africa., Porterfield JZ; Africa Health Research Institute (AHRI), Durban, South Africa.; Department of Otolaryngology-Head & Neck Surgery, Division of Infectious Diseases, University of Kentucky, Lexington, KY, United States.; Department of Microbiology, Immunology and Molecular Genetics, - Division of Infectious Diseases, University of Kentucky, Lexington, KY, United States.; Department of Internal Medicine - Division of Infectious Diseases, University of Kentucky, Lexington, KY, United States., Sibiya AL; Department of Otorhinolaryngology & Head & Neck Surgery, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, Durban, South Africa., Bipath R; Department of Otorhinolaryngology, King Edward VIII hospital, University of KwaZulu-Natal, Durban, South Africa., Moodley K; Department of Ear Nose and Throat, General Justice Gizenga Mpanza Regional Hospital (Stanger Hospital), University of KwaZulu-Natal, Durban, South Africa., Kuhn W; Department of Otorhinolaryngology & Head & Neck Surgery, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, Durban, South Africa.; Department of Ear Nose and Throat, General Justice Gizenga Mpanza Regional Hospital (Stanger Hospital), University of KwaZulu-Natal, Durban, South Africa., Berger B; Computer Science & Artificial Intelligence Lab and Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA, United States., Nguyen S; Institute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States., de Oliveira T; KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa., Ndung'u T; Africa Health Research Institute (AHRI), Durban, South Africa.; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu Natal, Durban, South Africa.; University College London, Division of Infection and Immunity, London, United Kingdom., Goulder P; Africa Health Research Institute (AHRI), Durban, South Africa.; HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu Natal, Durban, South Africa.; Department of Paediatrics, University of Oxford, Oxford, United Kingdom., Shalek AK; Institute for Medical Engineering & Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, United States.; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, United States.; Ragon Institute of MGH, Harvard, Cambridge, MA, United States., Leslie A; Africa Health Research Institute (AHRI), Durban, South Africa.; University College London, Division of Infection and Immunity, London, United Kingdom., Kløverpris HN; Africa Health Research Institute (AHRI), Durban, South Africa.; Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.; University College London, Division of Infection and Immunity, London, United Kingdom.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2022 Oct 18; Vol. 13, pp. 912038. Date of Electronic Publication: 2022 Oct 18 (Print Publication: 2022).
DOI: 10.3389/fimmu.2022.912038
Abstrakt: Lymphoid tissues are an important HIV reservoir site that persists in the face of antiretroviral therapy and natural immunity. Targeting these reservoirs by harnessing the antiviral activity of local tissue-resident memory (T RM ) CD8 + T-cells is of great interest, but limited data exist on T RM -like cells within lymph nodes of people living with HIV (PLWH). Here, we studied tonsil CD8 + T-cells obtained from PLWH and uninfected controls from South Africa. We show that these cells are preferentially located outside the germinal centers (GCs), the main reservoir site for HIV, and display a low cytolytic and a transcriptionally T RM -like profile distinct from blood CD8 + T-cells. In PLWH, CD8 + T RM -like cells are expanded and adopt a more cytolytic, activated, and exhausted phenotype not reversed by antiretroviral therapy (ART). This phenotype was enhanced in HIV-specific CD8 + T-cells from tonsils compared to matched blood suggesting a higher antigen burden in tonsils. Single-cell transcriptional and clonotype resolution showed that these HIV-specific CD8 + T-cells in the tonsils express heterogeneous signatures of T-cell activation, clonal expansion, and exhaustion ex-vivo. Interestingly, this signature was absent in a natural HIV controller, who expressed lower PD-1 and CXCR5 levels and reduced transcriptional evidence of T-cell activation, exhaustion, and cytolytic activity. These data provide important insights into lymphoid tissue-derived HIV-specific CD8 + T RM -like phenotypes in settings of HIV remission and highlight their potential for immunotherapy and targeting of the HIV reservoirs.
Competing Interests: AKS reports compensation for consulting and/or SAB membership from Merck, Honeycomb Biotechnologies, Clarity, Repertoire Immune Medicines, Ochre Bio, Third Rock Ventures, Hovione, Relation Therapeutics, FL82, Empress Therapeutics, and Dahlia Biosciences. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Fardoos, Nyquist, Asowata, Kazer, Singh, Ngoepe, Giandhari, Mthabela, Ramjit, Singh, Karim, Buus, Anderson, Porterfield, Sibiya, Bipath, Moodley, Kuhn, Berger, Nguyen, de Oliveira, Ndung’u, Goulder, Shalek, Leslie and Kløverpris.)
Databáze: MEDLINE
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