Interleukin-7-Dependent Production of RANTES That Correlates with Human Immunodeficiency Virus Disease Progression

Abstract

There is a relationship between CD4-T-cell number and circulating interleukin 7 (IL-7) levels in human immunodeficiency virus (HIV)-positive individuals. Here, we show that IL-7 induced a dose-dependent production of CCL3 (MIP-1α), CCL4 (MIP-1β), and CCL5 (RANTES) in peripheral blood mononuclear cells (PBMC), ex vivo tonsil lymphoid tissue of HIV ⁻ individuals, and PBMC from HIV ⁺ individuals, suggesting that IL-7 may regulate β-chemokine production in vivo. In a cross-sectional study of HIV ⁺ individuals ( n = 130), a weak but significant correlation between IL-7 and RANTES was noted ( r = 0.379; P < 0.001). Remarkably, the correlation between IL-7 and RANTES increased to an r value of 0.798 ( P < 0.001) if individuals with low CD4 cell counts (<200 cells/μl) were excluded from the analysis. Our results suggest that there is a relationship between IL-7 and the production of RANTES both in vitro and in vivo that is lost in immune-compromised patients (CD4 count of <200 cells/μl) but that could be restored by antiretroviral therapy. Unlike the case for IL-7, high levels of RANTES suggest an intermediate stage of HIV disease progression.