Abstract
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.
Highlights
The hallmark of HIV-1 infection is a progressive reduction of CD4 T cells
Regulatory T cells (Treg) represent a subgroup of T lymphocytes with immunosuppressive activities that can reduce HIV-1 associated immune activation, but may worsen HIV-1 disease progression by inhibiting T cell responses directed against HIV-1 itself
We describe a non-classical population of regulatory T cells that differ from conventional Treg by the expression of HLA-G, a molecule that contributes to maternal tolerance against semiallogeneic fetal tissue during pregnancy
Summary
The hallmark of HIV-1 infection is a progressive reduction of CD4 T cells. The main function of these cells is to provide antigenspecific helper cell activity against a wide panel of microbial antigens, some of these cells have regulatory immunosuppressive activities. During progressive HIV-1 infection, the relative frequency of classical Treg is increased, while their absolute counts are reduced as a consequence of lower total CD4 T cell counts [4]. This indicates that classical Treg decline at a slower rate than conventional CD4 T cells during progressive HIV-1 infection, and suggests that these cells may play an important role in the immune pathogenesis of HIV-1 infection. Classical Treg may have beneficial effects on HIV-1 disease progression by reducing the deleterious consequences of HIV-1 associated immune activation [7,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
