Acute upregulation of CCR-5 expression by CD4+ T lymphocytes in HIV-infected patients treated with interleukin-2. ANRS 048 IL-2 Study Group

• Published in: AIDS (London) Vol. 13; no. 4; pp. 455 - 463
• Main Authors: Zou, W, Foussat, A, Houhou, S, Durand-Gasselin, I, Dulioust, A, Bouchet, L, Galanaud, P, Levy, Y, Emilie, D
• Format: Journal Article
• Language: English
• Published: England 11.03.1999
• Subjects: Adult; AIDS/HIV; CD4-Positive T-Lymphocytes - classification; CD4-Positive T-Lymphocytes - immunology; Female; Gene Expression Regulation; HIV Infections - drug therapy; HIV Infections - immunology; Humans; Interleukin-2 - administration & dosage; Interleukin-2 - immunology; Interleukin-2 - therapeutic use; Male; Middle Aged; Receptors, CCR5 - genetics; Receptors, CCR5 - immunology
• ISSN: 0269-9370

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. To evaluate the acute effect of IL-2 on circulating T-lymphocyte subpopulations and their expression of chemokine receptors. 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. 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. 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.