title: Elevated effector cell sensitivity to Treg-cell suppression that is not associated with reduced Th17-cell expression distinguishes HIV+ asymptomatic subjects from progressors.
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.
authors: Department of Infectious Diseases, King's College London, Borough Wing, Guys' Hospital, London, England, UK.
authors: Georgina S
authors: GS
authors: Thorborn
authors: Laura
authors: L
authors: Pomeroy
authors: Heidi
authors: H
authors: Ishohanni
authors: Barry S
authors: BS
authors: Peters
authors: Annapurna
authors: A
authors: Vyakarnam
mesh_terms: D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D018450:Disease Progression; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000821:virology
chemical_list: C508017:IL2RA protein, human; D020381:Interleukin-17; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D007371:Interferon-gamma