Abstract

BackgroundThe acute phase of HIV infection is characterized by massive depletion of CD4 T cells, high viral plasma levels and pronounced systemic immune activation. Regulatory T cells (Tregs) have the potential to control systemic immune activation but also to suppress antigen specific T and B cell response. The co-expression of FoxP3 and Helios transcription factors, has been described for identification of highly suppressive Tregs. The aim of this study was to characterize the phenotype of classic Tregs during early HIV infection, and to assess the correlations between the frequencies and phenotype of Tregs with the plasma viral load, CD4 counts, immune activation and the frequency of antibodies reactive to HIV-1 proteins, measured by an immunochromatographic test.ResultsThe relative frequency of classic Tregs cells in peripheral blood correlated positively with HIV viral load and immune activation of CD8 T cells, and inversely with absolute CD4 counts and development of anti-HIV antibodies in subjects with early HIV infection. However, the expression of Helios in classic Tregs was inversely correlated with viral replication and immune activation, and positively with recovery of CD4 T cell counts and appearance of antibodies reactive to HIV-1 proteins.ConclusionThese results raise the hypothesis that classic Tregs are inefficient at controlling systemic immune activation in subjects with early HIV infection and may be associated with delayed production of antibodies against HIV proteins, delaying the control of viral replication. Conversely, Helios expressing Tregs might contribute to control of viral replication by mechanisms involving the limitation of systemic immune activation.

Highlights

  • The acute phase of HIV infection is characterized by massive depletion of CD4 T cells, high viral plasma levels and pronounced systemic immune activation

  • Since classic Regulatory CD4+ T cells (Tregs) are more effective in controlling antigen-specific immune responses, we evaluated their association with humoral anti-HIV immune responses

  • Here we evaluated Helios+Tregs as CD4 +CD25HighFoxP3+Helios+ rather than memory Tregs identified as CD4+FoxP3+Helios+CD45RO+

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Summary

Introduction

The acute phase of HIV infection is characterized by massive depletion of CD4 T cells, high viral plasma levels and pronounced systemic immune activation. Regulatory T cells (Tregs) have the potential to control systemic immune activation and to suppress antigen specific T and B cell response. The co-expression of FoxP3 and Helios transcription factors, has been described for identification of highly suppressive Tregs. Classic Tregs have been characterized by high expression of the activation marker CD25, presence of the transcription factor Foxp or expression of low levels of the alpha chain of Interleukin-7 (IL-7) receptor, CD127 [2]. The co-expression of the transcription factors Helios and FoxP3 identifies highly suppressive Tregs, initially identified as natural Tregs [7, 8]

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