Different rates of CD4+and CD8+T-cell proliferation in interleukin-2-treated human immunodeficiency virus-positive subjects

Background: Interleukin-2 (IL-2) has been used successfully to increase CD4 cell counts in patients who are human immunodeficiency virus (HIV) positiv e. The mechanisms involved in this phenomenon are unknown. We hypothesized that a differential proliferation rate of CD4+ compared with CD8+ lymphocyt es could be related to the increase of CD4 counts and of CD4/CD8 ratios tha t occur in HIV+ patients during IL-2 treatment. Methods: We enrolled in our study 14 HIV+ patients treated with IL-2 or with highly active antiretrovi ral therapy (HAART) during a 96-week observation period. Using flow cytomet ry, we measured longitudinally the expression of the Ki67 antigen in periph eral blood CD4+ and CD8+ lymphocyte subsets. Results. Compared with HAART a lone, IL-2 produced a rapid increase of Ki67+ proliferating CD4 cells and a concomitant increase of the CD4/CD8 ratios, whereas the corresponding CD8 proliferation increased slightly. On the contrary, HAART alone was effectiv e in suppressing equally both CD4 and CD8 proliferation. Conclusions: Our r esults suggest a selective activity of IL-2 on CD4 T-cell proliferation; on the contrary, CD8-specific proliferation is affected minimally during trea tment. This information may offer the potential to plan correctly immune ac tivating regimens. (C) 2001 Wiley-Liss, Inc.