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

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. © 2013 li et al.