Functional characterization of HLA-G⁺ regulatory T cells in HIV-1 infection

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 -