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

Abstract

Interleukin (IL)-7 and its receptor (IL-7Ralpha) play important roles in regulating lymphopoiesis. Previous studies have reported that human immunodeficiency virus-1 (HIV-1) viraemia affects the expression of IL-7Ralpha, 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-7Ralpha 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-7Ralpha 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-7Ralpha; 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-7Ralpha 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-7Ralpha system and contributing to HIV-1 disease progression.

Fig. 1

A representative example of gating strategy identifying CD4⁺ and CD8⁺ T cell subsets expressing interleukin-7 receptor (CD127). Naive (CD45RA⁺ CCR7⁺ CD27⁺), central memory (CM; CD45RA^– CCR7⁺ CD27⁺), preterminal effector (PTE; CD45RA^– CCR7^– CD27^–) and terminal effector (TE; CD45RA⁺ CCR7^– CD27^–) CD4⁺ and CD8⁺ cell subsets.

Fig. 2

Expression of interleukin-7 receptor (IL-7Rα) on naive (a), central memory (b), preterminal effector (c) and terminal effector (d) CD4⁺ and CD8⁺ T cells by study group. The mean, standard error of the mean and P-values are shown.

Fig. 3

Expression of activation markers [CD38/human leucocyte antigen D-related (HLA-DR)] on naive (a), central memory (b), preterminal effector (c) and terminal effector (d) CD4⁺ and CD8⁺ T cells by study group. The mean, standard error of the mean and P-values are shown.

Fig. 4

Circulating levels of interleukin-7 levels by study group. The medians and P-values are shown.

Fig. 5

Inverse relationships between central memory CD4⁺ or CD8⁺ T cells expressing interleukin-7 receptor (IL-7Rα) and those expressing activation markers [CD38/human leucocyte antigen D-related (HLA-DR)] in the entire study population. (a) Correlation between CM CD4⁺ cells expressing IL-7Rα and those expressing CD38/HLA-DR. (b) Correlation between CM CD8⁺ cells expressing IL-7Rα and those expressing CD38/HLA-DR. Spearman's correlation coefficients and P-values are shown.