TIGIT is upregulated by HIV-1 infection and marks a highly functional adaptive and mature subset of natural killer cells
TIGIT is upregulated by HIV-1 infection and marks a highly functional adaptive and mature subset of natural killer cells
ABSTRACT ObjectiveOur objective was to investigate the mechanisms that govern natural killer (NK) cell responses to HIV, with a focus on specific receptor-ligand interactions involved in HIV recognition by NK cells. Design and MethodsWe first performed a mass cytometry-based screen of NK cell receptor expression patterns in healthy controls and HIV+ individuals. We then focused mechanistic studies on the expression and function of T cell immunoreceptor with Ig and ITIM domains (TIGIT). ResultsThe mass cytometry screen revealed that TIGIT is upregulated on NK cells of untreated HIV+ women, but not in antiretroviral-treated women. TIGIT is an inhibitory receptor that is thought to mark exhausted NK cells; however, blocking TIGIT did not improve anti-HIV NK cell responses. In fact, the TIGIT ligands CD112 and CD155 were not upregulated on CD4+ T cells in vitro or in vivo, providing an explanation for the lack of benefit from TIGIT blockade. TIGIT expression marked a unique subset of NK cells that express significantly higher levels of NK cell activating receptors (DNAM-1, NTB-A, 2B4, CD2) and exhibit a mature/adaptive phenotype (CD57hi, NKG2Chi, LILRB1hi, FcRγlo, Syklo). Furthermore, TIGIT+ NK cells had increased responses to mock-infected and HIV-infected autologous CD4+ T cells, and to PMA/ionomycin, cytokine stimulation and the K562 cancer cell line. ConclusionsTIGIT expression is increased on NK cells from untreated HIV+ individuals. Although TIGIT does not participate directly in NK cell recognition of HIV, it marks a population of mature/adaptive NK cells with increased functional responses.
Ranganath Thanmayi、Alary Michel、Labb¨| Annie-Claude、Poudrier Johanne、Blish Catherine A.、Vergara Rosemary、Gu¨|dou Fernand、Vendrame Elena、Roger Michel、Zhao Nancy Q.、Holmes Susan、Seiler Christof
Department of Medicine, Division of Infection Diseases and Geographic Medicine, Stanford UniversityCentre de recherche du CHU de Qu¨|bec¨CUniversit¨| Laval D¨|partement de M¨|decine Sociale et Pr¨|ventive, Universit¨| Laval Institut National de Sant¨| Publique du Qu¨|becD¨|partement de Microbiologie, Infectiologie et Immunologie de l??Universit¨| de Montr¨|al D¨|partement de Microbiologie M¨|dicale et InfectiologieLaboratoire d?ˉImmunog¨|n¨|tique, Centre de Recherche du Centre Hospitalier de l?ˉUniversit¨| de Montr¨|al (CRCHUM) D¨|partement de Microbiologie, Infectiologie et Immunologie de l??Universit¨| de Montr¨|alDepartment of Medicine, Division of Infection Diseases and Geographic Medicine, Stanford University||Immunology Program, Stanford University||Chan Zuckerberg BiohubDepartment of Medicine, Division of Infection Diseases and Geographic Medicine, Stanford UniversityDispensaire ISTDepartment of Medicine, Division of Infection Diseases and Geographic Medicine, Stanford UniversityLaboratoire d?ˉImmunog¨|n¨|tique, Centre de Recherche du Centre Hospitalier de l?ˉUniversit¨| de Montr¨|al (CRCHUM) D¨|partement de Microbiologie, Infectiologie et Immunologie de l??Universit¨| de Montr¨|alDepartment of Medicine, Division of Infection Diseases and Geographic Medicine, Stanford University||Immunology Program, Stanford UniversityDepartment of Statistics, Stanford UniversityDepartment of Statistics, Stanford University
基础医学生物科学研究方法、生物科学研究技术
TIGITNK cellsHIVadaptivemature
Ranganath Thanmayi,Alary Michel,Labb¨| Annie-Claude,Poudrier Johanne,Blish Catherine A.,Vergara Rosemary,Gu¨|dou Fernand,Vendrame Elena,Roger Michel,Zhao Nancy Q.,Holmes Susan,Seiler Christof.TIGIT is upregulated by HIV-1 infection and marks a highly functional adaptive and mature subset of natural killer cells[EB/OL].(2025-03-28)[2025-04-27].https://www.biorxiv.org/content/10.1101/764217.点此复制
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