HIV-infected long-term nonprogressors display a unique correlative pattern between the interleukin-7/interleukin-7 receptor circuit and T-cell homeostasis

Background We hypothesized that there may be a correlation between the interleukin-7 (IL-7)/IL-7 receptor (IL-7R) regulatory system and parameters of T-cell homeostasis in HIV-infected long-term nonprogressors (LTNPs) as compared with patients with disease progression. Methods The possibility of a correlation between T-cell homeostatic parameters and IL-7/IL-7R was investigated in 22 LTNPs (CD4 count >= 500 cells/mu L for > 10 years) vs. HIV-positive patients at different disease stages [12 early: CD4 count >= 400 cells/mu L; 15 late (AIDS-presenters): CD4 count < 150 cells/mu L]. Results Compared with early-stage HIV-positive patients, LTNPs displayed a higher circulating IL-7 concentration (P=0.05), which was positively associated with higher IL-7R alpha expression and a higher T-cell receptor excision circle (TREC) content specifically within CD4 cells (P < 0.05). Compared with late-stage disease patients, early-stage disease patients displayed a lower IL-7 concentration (P < 0.01) and higher percentages of IL-7R alpha(+) CD4 and CD8 cells (P=0.05). IL-7 was positively correlated with the percentage of TREC+ CD4 cells (P < 0.01), which translated into a higher percentage of naive CD4 cells in early-stage disease patients than in late-stage disease patients; however, the CD4 cells in early-stage disease patients were less enriched in recent thymic emigrants (RTEs) compared with LTNPs (P < 0.05). In late-stage AIDS-developing patients, substantially increased IL-7 was correlated with a decreased percentage of IL-7R alpha(+) CD4 cells (P=0.01), which resulted in these patients having a significantly lower percentage of naive T cells (P < 0.01) and a significantly lower content of TREC (P < 0.01) than the other patients. Conclusions The maintenance of high CD4 cell counts in LTNPs was associated with a specific IL-7/IL-7R pattern characterized by increased IL-7 and highest IL-7R alpha-expressing CD4 cells relative to other patients. Compared with patients with late-stage disease, LTNPs displayed a phenotypically naive, less activated CD4 cell pool highly enriched in RTEs, suggesting the existence of a compensatory IL-7-mediated pathway specifically sustaining peripheral CD4 counts.