Loss of CD127 Expression Defines an Expansion of Effector CD8+ T Cells in HIV-Infected Individuals

Abstract

The immunodeficiency that follows HIV infection is related to the virus-mediated killing of infected CD4+ T cells, the chronic activation of the immune system, and the impairment of T cell production. In this study we show that in HIV-infected individuals the loss of IL-7R (CD127) expression defines the expansion of a subset of CD8+ T cells, specific for HIV as well as other Ags, that show phenotypic (i.e., loss of CCR7 and CD62 ligand expression with enrichment in activated and/or proliferating cells) as well as functional (i.e., production of IFN-γ, but not IL-2, decreased ex vivo proliferative potential and increased susceptibility to apoptosis) features of effector T cells. Importantly, in HIV-infected individuals the levels of CD8+CD127− T cells are directly correlated with the main markers of disease progression (i.e., plasma viremia and CD4+ T cell depletion) as well as with the indices of overall T cell activation. In all, these results identify the expansion of CD8+CD127− effector-like T cells as a novel feature of the HIV-associated immune perturbation. Further studies are thus warranted to determine whether measurements of CD127 expression on CD8+ T cells may be useful in the clinical management of HIV-infected individuals.

IL‐7Rα expression on CD4+ T lymphocytes decreases with HIV disease progression and inversely correlates with immune activation

“…The most recent of these studies has correlated reduced receptor levels with T cells depletion and immune activation; however, the focus of this study was CD8 + T cell population, not CD4 + T cells [40]. Here, we report not only a loss of receptor expression on the CD4 + T cells of HIV-positive individuals, but find expression of IL-7Ra is inversely correlated with immune activation, and levels of ex vivo apoptosis, and positively correlated with CD4 counts in both bivariate and multivariate analysis correcting for HIV status.…”

“…The majority of studies evaluating IL-7R expression in HIV-positive individuals have reported a reduced expression of IL-7R on the entire CD4 + and CD8 + T cell populations, and have not assessed the level of T cell activation, apoptosis, or defined the specific T cell subset in which the reduction was most pronounced [35][36][37][38][39][40]. The most recent of these studies has correlated reduced receptor levels with T cells depletion and immune activation; however, the focus of this study was CD8 + T cell population, not CD4 + T cells [40].…”

“…More recently, the loss of this receptor on CD8 + T cells of HIV-positive individuals was shown to correlate with markers of disease progression such as T cell activation, plasma viremia, and CD4 T cell depletion [40]. However, it remains unknown whether levels of IL-7R on CD4 + T cells are associated with HIV disease progression, apoptosis, or factors influencing progression such as immune activation.…”

Immunosenescence and hurdles in the clinical management of older HIV-patients

“…[140][141][142][143] IL-7 is another key cytokine which role is impaired in HIV infection, mostly thank to impairment of receptor signaling via CD127 (a component of IL-7 receptor [IL-7R]). [144][145] IL-7 is crucial for T cell development and homeostasis thanks to its anti-apoptotic and co-stimulatory proliferative signals 146 and in untreated patients with HIV infection high levels of IL-7 reflects a compensatory loop mechanism to contrast HIV-induced lymphopenia (Fig. 2).…”

Assessment of HIV infection in cells of infected individuals

“…T cells [PAIARDINI et al, 2005] following the general trend of systemic HIV-1 activity, but also that MS mRNA levels in PBMCs are closely associated with the number of productively infected cells, because the half-life of this class of transcripts after administration of a potent protease inhibitor is very consistent with that of productively infected cells.…”