Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
Acute upregulation of CCR-5 expression by CD4+ T lymphocytes in HIV-infected patients treated with interleukin-2. ANRS 048 IL-2 Study Group.
AIDS. 1999 Mar 11;13(4):455-63. Unique Identifier : AIDSLINE MED/99211230 Zou W; Foussat A; Houhou S; Durand-Gasselin I; Dulioust A; Bouchet L; Galanaud P; Levy Y; Emilie D; INSERM U131, Institut Paris-Sud sur les Cytokines and Service de; Medecine Interne et d'Immunologie Clinique, Hopital Antoine; Beclere, Clamart, France.
Abstract:
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.
Keywords: JOURNAL ARTICLE Adult CD4-Positive T-Lymphocytes/CLASSIFICATION/*IMMUNOLOGY Female Gene Expression Regulation Human HIV Infections/DRUG THERAPY/*IMMUNOLOGY Interleukin-2/ADMINISTRATION & DOSAGE/*IMMUNOLOGY/THERAPEUTIC USE Male Middle Age Receptors, CCR5/GENETICS/*IMMUNOLOGY Support, Non-U.S. Gov't 990830
A9980990
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