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

Abstract

Many factors can influence the rate of HIV disease progression, including those that maintain T cell homeostasis. One key homeostatic regulator is the IL‐7 receptor (IL‐7R). Previous studies have shown IL‐7R expression levels decrease in HIV infection, but effects on memory subtypes, CD4+ T cells, and cell function have not been explored. The present study examined the expression of the IL‐7Rα chain on naïve and memory T lymphocyte subsets of both HIV‐positive and HIV‐negative individuals from Nairobi, Kenya to assess the role of IL‐7Rα in HIV disease. Expression of IL‐7Rα was significantly reduced in all CD4+ and CD8+ T cell subsets in HIV‐positive individuals. This reduction was further enhanced in those with advanced HIV progression. Expression of IL‐7Rα was inversely correlated to immune activation, and apoptosis, and was positively correlated with CD4 count in both bivariate and multivariate analysis. Expression of IL‐7Rα did not correlate with HIV viral loads, indicating the elevated immune activation seen in HIV‐infected individuals may be impacting expression of IL‐7Rα, independent of viral loads. Signaling via the IL‐7R is essential for T cell homeostasis and maintenance of T cell memory. Reduction of this receptor may contribute to the homeostatic disruption seen in HIV.

Effect of Antiretroviral Therapy on Apoptosis Markers and Morphology in Peripheral Lymph Nodes of HIV-Infected Individuals

“…For example, although Bcl-2 was found to be expressed in peripheral T-lymphocytes and strongly correlated with spontaneous T cell apoptosis [32][33][34][35], in lymph nodes, Bcl-2 was detected primarily in the B (mantle zone of the germinal centers) and not in the T cell area. Similarly, IL-7Ra was found to be expressed on peripheral T and B cells, and peripheral CD4+ T cell depletion correlated well with the down-regulation of IL-7Ra [36,37]. In lymph nodes, IL-7Ra which increased after therapy was detectable only in the germinal centers and not in the T cell area.…”

“…In lymph nodes, IL-7Ra which increased after therapy was detectable only in the germinal centers and not in the T cell area. The absence of IL-7Ra expression in the T cell area resembles those peripheral T cells in which a strong association of decreased IL-7Ra expression with low Bcl-2 expression has been found [36,37]. In lymph nodes, a significant down-regulation of TRAIL was found after therapy due primarily to the reduction of cells of the phagocytic type, whereas TRAIL was not identifiable in B or T lymphocytes.…”

The role of SNPs in the α-chain of the IL-7R gene in CD4+ T-cell recovery in HIV-infected African patients receiving suppressive cART

“…Third, immune activation (largely measured as increased expression of CD38 þ and HLA-DR þ on T-cells) has also been shown to be inversely correlated with IL-7Ra expression on CD4 T-cells in HIV-infected patients, 45,46 and immune activation has a negative impact on CD4 T-cell recovery. [47][48][49] Although we did not compare the immune activation levels in the UARTO and Caucasian patients, numerous studies have described a higher degree of immune activation both in HIVuninfected [50][51][52][53][54] and HIV-infected African patients [53][54][55][56] as compared with patients from high-income countries owing to differences in the environment 52 and prevalence of other co-infections.…”

In Vitro HIV Type 1 Infection Indirectly Alters CD127 Expression on CD8+ T Cells

“…[1][2][3] In HIV infection, we and others have demonstrated that CD127 is expressed on a lower proportion of CD4 + and CD8 + T cells compared to that observed in HIV-uninfected individuals. 2,4 Interleukin (IL)-7 activity is important for T cell development, homeostasis, memory development, and T cell effector functions. Despite the increase in IL-7 in HIV disease, 5 cytolytic T cell activity (CTL) becomes impaired with disease progression.…”

“…1 Impaired CD4 + and CD8 + T cell function and decreased CD127 expression have recently been linked to abnormal activation of the immune system in HIV + individuals and resulting immunodeficiency. 2 Expression of CD127 on both naive and memory CD8 + and CD4 + T cells has recently been shown to be inversely correlated with CD8 + T cell exhaustion in the context of persistent exposure to antigen 2 and the expansion of effector CD8 + T cells during chronic HIV infection. 8 The cellular mechanism linking antigen persistence to decreased CD127 expression is not known.…”