Persistent human immunodeficiency virus-1 antigenaemia affects the expression of interleukin-7Rα on central and effector memory CD4+ and CD8+ T cell subsets

Abstract

SummaryInterleukin (IL)-7 and its receptor (IL-7Ra) play important roles in regulating lymphopoiesis. Previous studies have reported that human immunodeficiency virus-1 (HIV-1) viraemia affects the expression of IL-7Ra, but its effects on CD4 + and CD8 + T cell memory subsets have not been studied. Using eight-colour flow cytometry, we compared the immunophenotypic patterns of CD4+ and CD8 + T cell subsets expressing IL-7Ra and activation markers, as well as circulating IL-7 levels, in three well-defined groups of HIV-1-infected subjects: successfully treated, viraemic and long-term non-progressor (LTNP). Compared with successfully treated and LTNP subjects, viraemic patients had reduced expression of IL-7Ra on both CD4+ and CD8 + T cells, particularly on central and effector memory T cell compartments, and substantially elevated expression of activation markers on CD8 + T cell subsets. Circulating IL-7 levels were correlated negatively with the number of CD4 + and CD8+ T cell subsets expressing IL-7Ra; these associations were stronger with CD4 + T cell subsets and mainly with central and effector memory cells. The expression of activation markers on CD4+ and CD8 + cell T subsets was not related to circulating IL-7 levels. A strong negative correlation was observed between central memory CD4 + or CD8 + T cells expressing IL-7Ra and those expressing activation markers, independently of IL-7 levels. Collectively, these results provide further insight on the role of unsuppressed viral load in disrupting the IL-7/IL-7Ra system and contributing to HIV-1 disease progression.

Dual Mechanism of Impairment of Interleukin-7 (IL-7) Responses in Human Immunodeficiency Virus Infection: Decreased IL-7 Binding and Abnormal Activation of the JAK/STAT5 Pathway

“…CD127 expression was decreased in the Mem subset of viremic patients (Fig. 3A), in agreement with published studies (22,27,41,54,70) and consistent with the notion of chronic immune activation in untreated HIV infection. CD127 expression was preserved in the Nv subset, except in one viremic patient, who showed a marked loss for this marker.…”

“…This differential regulation is thought to optimize utilization of ␥c family cytokines other than IL-7 by activated cells, while sparing limiting IL-7 resources for resting cells (62). CD127 expression is decreased and ␥c expression is increased in T cells from HIV-infected patients, consistent with changes associated with chronic immune activation (22,27,41,49,54,60,70,84). CD127 decrease is particularly marked in the memory CD8…”

“…ϩ T-cell subset of viremic patients with high levels of chronic immune activation, which may account for the perturbed IL-7 responses observed in this subset (11,22,41,49,54,60). However, it should be noted that decreased CD127 expression may be compensated for by increased ␥c expression and that the net effect of these changes on IL-7 binding capacity has not been investigated so far.…”

High expression levels of B lymphocyte stimulator (BLyS) by dendritic cells correlate with HIV-related B-cell disease progression in humans

“…Blood CD4 ϩ T-cell counts were determined as previously reported. 21 None of the study subjects had syphilis, hepatitis B, or hepatitis C. Informed consent was obtained from all subjects, and the research conformed to ethical guidelines of all authors' institutions.…”

Filarial Infection Modulates the Immune Response to Mycobacterium tuberculosis through Expansion of CD4+ IL-4 Memory T Cells

“…Models of chronic viral infection have provided some insights into the generation and persistence of various memory T cell populations (10, 11) and some phenotypic characterization of memory populations in humans with chronic filarial infections has been done previously (12). …”