Background. Interleukin (IL)-7 levels are increased in patients with human immunodeficiency virus type 1 (H1V-l)-associated lymphopenia; however, the effects of this on IL-7 receptor (IL-7R) expression, disease progression, and immune reconstitution remain unclear.

Methods. Plasma IL-7 levels were measured, by enzyme-linked immunoassay, in patients with primary, chronic, or long-term nonprogressive HIV-1 infection (PHI, CHI, and LTNP, respectively) before and after 40–48 weeks of antiretroviral therapy (ART). Cell-surface expression and intracellular expression of the IL-7R components CD127 and CD132 were measured by flow cytometry. The effects of IL-7 and cycloheximide on IL-7R expression by peripheral blood mononuclear cells were examined in vitro.

Results. Plasma IL-7 levels were increased in both patients with PHI and those with CHI; administration of ART resulted in normalized plasma IL-7 levels in patients with PHI but not in those with CHI. Plasma IL-7 levels positively correlated with CD4⁺ T cell immune reconstitution in patients with PHI. In vitro, exogenous IL-7 rapidly down-regulated cell-surface CD127 expression, but not CD132 expression, whereas subsequent reexpression required active protein synthesis. HIV-1 infection resulted in progressive decreases in the CD127⁺13⁻ subset and increases in the CD127⁻132⁺ subset of CD4⁺ and CD8⁺ T cells. Changes in CD4⁺ T cell expression of IL-7R components were evident in patients with LTNP who lost viral control, and these changes preceded increases in plasma IL-7 levels.

Conclusions. Perturbations in the IL-7/IL-7R system were clearly associated with disease progression but did not reliably predict immune reconstitution.