Functional characterization of HLA-G⁺ regulatory T cells in HIV-1 infection
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Functional characterization of HLA-G⁺ regulatory T cells in HIV-1 infection. / Li, Chun; Toth, Ilona; Schulze Zur Wiesch, Julian; Pereyra, Florencia; Rychert, Jennifer; Rosenberg, Eric S; van Lunzen, Jan; Lichterfeld, Mathias; Yu, Xu G.
in: PLOS PATHOG, Jahrgang 9, Nr. 1, 01.01.2013, S. e1003140.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Functional characterization of HLA-G⁺ regulatory T cells in HIV-1 infection
AU - Li, Chun
AU - Toth, Ilona
AU - Schulze Zur Wiesch, Julian
AU - Pereyra, Florencia
AU - Rychert, Jennifer
AU - Rosenberg, Eric S
AU - van Lunzen, Jan
AU - Lichterfeld, Mathias
AU - Yu, Xu G
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
KW - Biological Markers
KW - Bystander Effect
KW - CD8-Positive T-Lymphocytes
KW - Cell Count
KW - Cell Proliferation
KW - Cell Survival
KW - Disease Susceptibility
KW - HIV Infections
KW - HIV-1
KW - HLA-G Antigens
KW - Humans
KW - Immunity, Innate
KW - Immunophenotyping
KW - Leukocytes, Mononuclear
KW - Lymphocyte Activation
KW - T-Lymphocytes, Regulatory
U2 - 10.1371/journal.ppat.1003140
DO - 10.1371/journal.ppat.1003140
M3 - SCORING: Journal article
C2 - 23382678
VL - 9
SP - e1003140
JO - PLOS PATHOG
JF - PLOS PATHOG
SN - 1553-7366
IS - 1
ER -