HIV+ elite controllers have low HIV-specific T-cell activation yet maintain strong, polyfunctional T-cell responses

Abstract

Objective HIV+ elite controllers are a unique group of rare individuals who maintain undetectable viral loads in the absence of antiretroviral therapy. We studied immune responses in these subjects to inform vaccine development, with the goal of identifying the immune correlates of protection from HIV. Methods We compared markers of cellular activation, HIV-specific immune responses, and regulatory T (Treg) cell frequencies in 4 groups of subjects: HIV-negative healthy controls, elite controllers (HIV RNA level <75 copies/ml), individuals on highly active antiretroviral therapy (HAART), and subjects with HIV RNA level >10,000 copies/ml (non-controllers). Results Elite controllers possessed significantly lower levels of activated HIV-specific CD8+ T cells and of recently divided HIV-specific CD4+ T cells than non-controllers, while these differences were not seen in the respective CMV-specific T cell populations. Elite controllers also mounted a stronger and broader cytokine and chemokine response following HIV-specific stimulation than individuals on HAART and non-controllers. Finally, we found that HAART suppressed subjects had elevated Treg cell frequencies, while elite controllers and non-controllers maintained normal percentages of Treg cells. Conclusion Elite controllers maintain high levels of HIV-specific immune responses with low levels of HIV-specific T cell activation, and do not have elevated Treg cell levels. Based on these data an ideal HIV vaccine would induce strong HIV-specific immune responses while minimizing HIV-specific T cell activation.

Immunologic characteristics of HIV‐infected individuals who make broadly neutralizing antibodies

“…However, the circulating frequency of CD4 + Treg cells has not been found to show any correlation with the magnitude of HIV‐specific T‐cell responses,276, 277, 278 leaving the contribution of CD4 + Treg cells to regulation of virus‐specific T‐cell responses in HIV‐infected individuals unclear. Their role in suppressing immune activation is also uncertain.…”

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

“…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). On the other hand, Owen et al, showed that individuals on HAART had higher frequencies of Tregs compared to elite controllers (Owen, Heitman et al, 2010). In contrast yet again, more recent studies have demonstrated that elite controllers have a lower level of Treg cells compared to viremic individuals, but that this "low" level of Tregs is similar to that observed in HIV positive individuals with viral load controlled by HAART (Brandt, Benfield et al, 2011).…”

Polyfunctional T cells in human tuberculosis

“…Antiretroviral treatment (ART) during chronic HIV-1 infection results in a shift to a memory response composed of a polyfunctional phenotype that has also been observed in individuals who spontaneously control HIV-1 replication [8,9].…”