Li, ChunToth, IlonaSchulze zur Wiesch, JulianPereyra, FlorenciaRychert, Jennifer AnnRosenberg, Ericvan Lunzen, JanLichterfeld, MathiasYu, Xu2013-10-162013Li, Chun, Ilona Toth, Julian Schulze zur Wiesch, Florencia Pereyra, Jennifer Rychert, Eric S. Rosenberg, Jan van Lunzen, Mathias Lichterfeld, and Xu G. Yu. 2013. Functional characterization of hla-g+ regulatory t cells in hiv-1 infection. PLoS Pathogens 9(1): e1003140.1553-7366http://nrs.harvard.edu/urn-3:HUL.InstRepos:11179754Regulatory 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.en-USMedicineInfectious DiseasesViral DiseasesHIVRetrovirology and HIV immunopathogenesisJournal Article2013-10-1610.1371/journal.ppat.1003140