Functional Characterization of HLA-G+ Regulatory T Cells in HIV-1 Infection

PLoS Pathogens

Jennifer Rychert¹  Julian Schulze zur Wiesch¹  Florencia Pereyra²  Eric S. Rosenberg²  Mathias Lichterfeld³  Xu G. Yu⁴  Ilona Toth⁵  Chun Li⁶  Jan van Lunzen⁶ 

[1] Department of Internal Medicine, Section of Infectious Diseases, University Medical Center, Hamburg, Germany;Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany;Infectious Disease Division, Brigham and Women's Hospital, Boston, Massachusetts, United States of America;Infectious Disease Division, Massachusetts General Hospital, Boston, Massachusetts, United States of America;Program of Biological Sciences in Dental Medicine, Harvard University, Cambridge, Massachusetts, United States of America;Ragon Institute of MGH, MIT and Harvard University, Boston, Massachusetts, United States of America

关键词: T cells;    Regulatory T cells;    HIV-1;    Cytotoxic T cells;    Immune activation;    T helper cells;    Immune response;    Lymph nodes;   

DOI  :  10.1371/journal.ppat.1003140

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 CD25hi 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.

【 授权许可】

CC BY