CD4+FOXP3+ Regulatory T-Cell Subsets in Human Immunodeficiency Virus Infection

Abstract

The role of CD4+FOXP3+ regulatory T cells (Treg) in human immunodeficiency virus (HIV) infection has been an area of intensive investigation and remains a matter of ardent debate. Investigation and interpretation suffered from uncertainties concerning Treg quantification. Firstly, Treg quantification and function in HIV infection remain controversial in part because of the lack of reliable and specific markers to identify human Tregs. Secondly, analyzing Treg percentages or absolute numbers led to apparent discrepancies that are now solved: it is now commonly accepted that Treg are targets of HIV infection, but are preferentially preserved compared to conventional CD4 T cells. Moreover, the duality of immune defects associated to HIV infection, i.e., low grade chronic inflammation and defects in HIV-specific responses also casts doubts on the potential impact of Treg on HIV infection. Tregs may be beneficial or/and detrimental to the control of HIV infection by suppressing chronic inflammation or HIV-specific responses respectively. Indeed both effects of Treg suppression have been described in HIV infection. The discovery in recent years of the existence of phenotypically and functionally distinct human CD4+FOXP3+ Treg subsets may provide a unique opportunity to reconcile these contrasting results. It is tempting to speculate that different Treg subsets exert these different suppressive effects. This review summarizes available data concerning Treg fate during HIV infection when considering Treg globally or as subsets. We discuss how the identification of naïve and effector Treg subsets modulates our understanding of Treg biology during HIV infection and the potential impact of HIV infection on mechanisms governing peripheral differentiation of adaptive Tregs.

Continuous Antigenic Stimulation of DO11.10 TCR Transgenic Mice in the Presence or Absence of IL-1β: Possible Implications for Mechanisms of T Cell Depletion in HIV Disease

“…Such loss is associated with evidence that cells can begin to move through the cell cycle (i.e., express Ki67) but that they then do not divide (i.e., incorporate 2 H into new strands of DNA), as has been observed in the circulating cells of HIV-infected subjects by Sieg and colleagues (36). At the same time, there is a relative increase in CD4 + T REGS , as has also been observed in those infected with HIV (37). In the presence of IL-1β, by contrast, T cell division is enhanced in the spleen and peripheral LNs, consistent with a qualitatively distinct mechanism of T cell homeostasis.…”

LPS-treated bone marrow-derived dendritic cells induce immune tolerance through modulating differentiation of CD4+ regulatory T cell subpopulations mediated by 3G11 and CD127

“…Multiple subpopulations of CD4 + T regs were reported [30, 31]. For example, CD4 + CD25 + CD127 low T regs are necessary for blocking autoimmunity in vivo [32, 33].…”

The effect of cellular isolation and cryopreservation on the expression of markers identifying subsets of regulatory T cells

“…T regs are divided into different phenotypic and functional subsets (Simonetta and Bourgeois, 2013). For example, expression of CD120b (TNF-α receptor II) identifies a subset with high suppressive function (Mercer et al, 2010,Minigo et al, 2009,Chen et al, 2010).…”