title: Functional characterization of HLA-G⁺ regulatory T cells in HIV-1 infection.
abstract: Regulatory T cells represent a specialized subpopulation of T lymphocytes that may modulate spontaneous HIV-1 disease progression by suppressing immune activation or inhibiting antiviral T cell immune responses. While the effects of classical CD25(hi) FoxP3⁺ Treg during HIV-1 infection have been analyzed in a series of recent investigations, very little is known about the role of non-classical regulatory T cells that can be phenotypically identified by surface expression of HLA-G or the TGF-β latency-associated peptide (LAP). Here, we show that non-classical HLA-G-expressing CD4 Treg are highly susceptible to HIV-1 infection and significantly reduced in persons with progressive HIV-1 disease courses. Moreover, the proportion of HLA-G⁺ CD4 and CD8 T cells was inversely correlated to markers of HIV-1 associated immune activation. Mechanistically, this corresponded to an increased ability of HLA-G⁺ Treg to reduce bystander immune activation, while only minimally inhibiting the functional properties of HIV-1-specific T cells. Frequencies of LAP⁺ CD4 Treg were not significantly reduced in HIV-1 infection, and unrelated to immune activation. These data indicate an important role of HLA-G⁺ Treg for balancing bystander immune activation and anti-viral immune activity in HIV-1 infection and suggest that the loss of these cells during advanced HIV-1 infection may contribute to immune dysregulation and HIV-1 disease progression.
authors: Ragon Institute of MGH, MIT and Harvard University, Boston, Massachusetts, United States of America.
authors: Chun
authors: C
authors: Li
authors: Ilona
authors: I
authors: Toth
authors: Julian
authors: J
authors: Schulze Zur Wiesch
authors: Florencia
authors: F
authors: Pereyra
authors: Jennifer
authors: J
authors: Rychert
authors: Eric S
authors: ES
authors: Rosenberg
authors: Jan
authors: J
authors: van Lunzen
authors: Mathias
authors: M
authors: Lichterfeld
authors: Xu G
authors: XG
authors: Yu
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D024201:Bystander Effect / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002452:Cell Count; D049109:Cell Proliferation; D002470:Cell Survival; D004198:Disease Susceptibility; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1; D059951:HLA-G Antigens / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000821:virology
chemical_list: D015415:Biomarkers; D059951:HLA-G Antigens
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