Increased plasma interleukin-7 level correlates with decreased CD127 and increased CD132 extracellular expression on T cell subsets in patients with HIV-1 infection

Abstract

Background. Interleukin (IL)-7 levels are increased in patients with human immunodeficiency virus type 1 (HIV-1)-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 +132- 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. © 2006 by the Infectious Diseases Society of America. All rights reserved.