Increased Turnover of FoxP3high Regulatory T Cells Is Associated With Hyperactivation and Disease Progression of Chronic HIV-1 Infection

Abstract

Turnover level of Treg was increased in HIV-1-infected subjects, which is associated with immune hyperactivation and the disease progression, and may serve as a surrogate marker to predict HIV-1 disease progression.

Impact of HIV Infection and HAART Therapy on CD4 T Helper Cell Subset Expression and Function

“…This point is also supported by a report showing that recombinant IL-2 treatment in a phase III trial actually enhanced Treg populations, possibly explaining why this treatment failed to elicit better clinical outcome (Weiss, Letimier et al, 2010). Treg depletion has been associated with an increase in immune activation (Eggena, Barugahare et al, 2005) and several important studies have demonstrated correlation of Treg proliferation and turnover with lower CD4 counts (Bi, Suzuki et al, 2009;Piconi, Trabattoni et al, 2010;Xing, Fu et al, 2010). Interestingly, elite controllers, a rare population of individuals that can maintain undetectable HIV viral loads in the absence of HAART, demonstrated higher frequencies of Treg cells compared to individuals on HAART (Chase, Yang et al, 2008).…”

Homeostasis and Function of Regulatory T Cells in HIV/SIV Infection

“…In agreement with this hypothesis, we and other groups have reported increased Ki67 expression in circulating Tregs from untreated, chronically infected patients. This increase was controlled by HAART (12, 50,71,98). Of note, a direct effect of HIV on Treg expansion has been hypothesized, as direct interaction of HIV with Tregs induced their expansion and promoted the expression of FOXP3, CD25, and CTLA-4 (3).…”

The split personality of regulatory T cells in HIV infection

“…Most studies suggest that treatment is able to significantly decrease or even normalize Treg frequency at levels similar to that of healthy donors, at least in patients with successful ART. 15,36,37,42,54 Moreover, in most cross-sectional studies, peripheral Treg frequency was reported to be lower in ART-treated patients compared with untreated, chronically infected patients. 15,40,41,44 Interestingly, Treg frequency remained higher in patients who did not respond to treatment, that is, immunologic 55 or virologic 40 nonresponders, compared with full responders.…”