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

Blood. 2002 Sep 15;100(6):2159-67.


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 beta and gamma 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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • Case-Control Studies
  • 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


  • IL2RA protein, human
  • IL2RB protein, human
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-2 Receptor beta Subunit
  • Receptors, Interleukin
  • Receptors, Interleukin-2