Acute upregulation of CCR-5 expression by CD4+ T lymphocytes in HIV-infected patients treated with interleukin-2

Background: The treatment of HIV-infected patients with interleukin (IL)-2 causes a sustained increase in CD4+ T-lymphocyte counts, involving both naive and memory cells. However, the short-term immunological effects of IL-2, which may shed light on the mechanism of immune reconstitution by this cytokine, are unknown. Objective: To evaluate the acute effect of IL-2 on circulating T-lymphocyte subpopulations and their expression of chemokine receptors. Design and methods: Flow cytometry, reverse transcriptase polymerase chain reaction and chemokine receptor function experiments were performed before and after 5 days of IL-2 administration in 30 HIV-infected patients. Results: IL-2 induced an acute lymphopenia of both naive and memory T-helper (TH) lymphocytes. This was associated with a large increase in CC-chemokine receptor (CCR)-5 and CCR-2b expression by TH cells. Before IL-2 treatment, CCR-5 was mostly produced by CD62L- memory TH lymphocytes. After 5 days of IL-2 administration, the level of CCR-5 mRNA in circulating cells was 18.6 times higher than before treatment (P < 0.002). CCR-5 expression was upregulated in CD62L-memory TH lymphocytes, but also in CD62L+ memory and in naive (CD62L+ CD45RO-) TH lymphocytes. IL-2 treatment also increased the function of CCR-5 in TH cells. Conclusions: Chemokine receptors are involved in trafficking of lymphocytes. The IL-2-induced upregulation of chemokine receptors in TH cells may thus play a role in the acute effects of this cytokine in TH lymphocyte redistribution. (C) 1999 Lippincott Williams & Wilkins.