SEARCH

SEARCH BY CITATION

Keywords:

  • HIV;
  • IL-17;
  • Treg cells

Abstract

Suppression mediated by Treg cells is a balance between Treg-cell suppressive potency versus sensitivity of effector cells to Treg-cell suppression. We assessed if this balance, along with Treg-cell number relative to the Treg-cell counter-regulatory cytokine IL-17, differs between asymptomatic HIV+ subjects versus those who progress onto disease. Cross-over studies comparing Treg-cell potency, measured by effector cell proliferation or IFN-γ expression, from HIV-infected versus control subjects to suppress the proliferation of allogeneic control effector cells demonstrated increased sensitivity of CD4+CD25 effector cells from asymptomatic HIV+ subjects to suppression, rather than an increase in the suppressive potential of their CD4+CD25+ Treg cells. In contrast, HIV+ progressors did not differ from controls in Treg-cell potency or effector cell sensitivity to Treg-cell suppression. Both CD4+CD25+Foxp3+ Treg and effector IL-17 absolute cell numbers were significantly lower in all HIV+ subjects tested and not restored by antiviral therapy. Thus, these novel data suggest that elevated Treg-cell-mediated suppression due to increased sensitivity of effectors to Treg cells may be a natural host response in chronic asymptomatic HIV infection, which is lost as disease progresses and that this feature of CD25 effector cells is not inextricably linked to reduced production of the Treg-cell counter-regulatory cytokine IL-17.