Interleukin-2 induced immune effects in human immunodeficiency virus-infected patients receiving intermittent interleukin-2 immunotherapy

Eur J Immunol. 2001 May;31(5):1351-60. doi: 10.1002/1521-4141(200105)31:5<1351::AID-IMMU1351>3.0.CO;2-9.

Abstract

To characterize the immunological effects of intermittent IL-2 therapy, which leads to selective increases in CD4+ T lymphocytes in HIV-infected patients, 11 patients underwent extensive immunological evaluation. While IL-2 induced changes in both CD4+ and CD8+ cell number acutely, only CD4+ cells showed sustained increases following discontinuation of IL-2. Transient increases in expression of the activation markers CD38 and HLA-DR were seen on both CD4+ and CD8+ cells, but CD25 (a chain of the IL-2 receptor) increased exclusively on CD4+ cells. This increase in CD25 expression was sustained for months following discontinuation of IL-2, and was seen in naive as well as memory cells. IL-2 induced cell proliferation, but tachyphylaxis to these proliferative effects developed after 1 week despite continued IL-2 administration. It thus appears that sustained CD25 expression selectively on CD4+ cells is a critical component of the immunological response to IL-2, and that intermittent administration of IL-2 is necessary to overcome the tachyphylaxis to IL-2-induced proliferation.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1
  • Adult
  • Antigens, CD*
  • Antigens, Differentiation / metabolism
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Division / drug effects
  • Flow Cytometry
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HLA-DR Antigens / metabolism
  • Humans
  • Immunologic Memory / immunology
  • Immunotherapy*
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / immunology*
  • Interleukin-2 / pharmacology
  • Interleukin-2 / therapeutic use*
  • Lymphocyte Activation / drug effects
  • Lymphocyte Subsets / drug effects
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Male
  • Membrane Glycoproteins
  • NAD+ Nucleosidase / metabolism
  • Receptors, Interleukin-2 / metabolism
  • Tachyphylaxis
  • Time Factors

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • HLA-DR Antigens
  • Interleukin-2
  • Membrane Glycoproteins
  • Receptors, Interleukin-2
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • NAD+ Nucleosidase
  • ADP-ribosyl Cyclase 1