Long-term effects of intermittent interleukin 2 therapy in patients with HIV infection: characterization of a novel subset of CD4+/CD25+ T cells

• Published in: Blood 2002-09, Vol.100 (6), p.2159-2167
• Main Authors: Sereti, Irini, Martinez-Wilson, Hector, Metcalf, Julia A., Baseler, Michael W., Hallahan, Claire W., Hahn, Barbara, Hengel, Richard L., Davey, Richard T., Kovacs, Joseph A., Lane, H. Clifford
• Format: Article
• Language: English
• Subjects: Adult; Antiretroviral Therapy, Highly Active; Case-Control Studies; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - metabolism; Cell Division - drug effects; Follow-Up Studies; HIV Infections - drug therapy; Humans; Interleukin-2 - pharmacology; Interleukin-2 - therapeutic use; Interleukin-2 Receptor alpha Subunit; Interleukin-2 Receptor beta Subunit; Killer Cells, Natural - metabolism; Middle Aged; Receptors, Interleukin - metabolism; Receptors, Interleukin-2 - drug effects; Receptors, Interleukin-2 - metabolism; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V100.6.2159

The long-term immunologic effects of intermittent interleukin 2 (IL-2) therapy were evaluated in a cross-sectional study by comparing 3 groups: HIV-seronegative volunteers, HIV-infected (HIV+) patients receiving highly active antiretroviral therapy (HAART), and HIV+ patients receiving HAART and intermittent IL-2. Whole-blood immunophenotyping was performed to study expression of the IL-2 receptor chains on T lymphocytes and natural killer cells and to further characterize CD4+/CD25+ T cells. Increased CD25 expression, especially in CD4+ T cells but also in CD8+ T cells, without increases in expression of the β and γ chains of the IL-2 receptor was detected in the IL-2 group. Up to 79% of naive CD4+ T cells (median, 61%) from patients in the IL-2 group expressed CD25, and the number of naive CD4+/CD25+ T cells correlated positively with both the total and naive CD4+ T-cell counts. A discrete population of CD45 double intermediate RA+/RO+CD4+ cells was also preferentially expanded in the IL-2 group, and the number of these cells strongly correlated with the total CD4+ count. Despite increases in CD25 expression, T lymphocytes from patients treated with IL-2 did not have increased expression of early (CD69) or late (CD95) activation markers or evidence of recent proliferation (Ki67). Both CD4+/CD25+ and CD4+/CD25− cells from IL-2–treated HIV+ patients proliferated in response to mitogens, specific antigens, and T-cell-receptor–mediated stimuli. Thus, intermittent administration of IL-2 in HIV+ patients leads to preferential expansion of a unique subset of CD4+ T cells that may represent a critical population in T-cell homeostasis.