Therapeutic Use of IL-2 to Enhance Antiviral T-cell Responses in Vivo

Nat Med. 2003 May;9(5):540-7. doi: 10.1038/nm866. Epub 2003 Apr 14.

Abstract

Interleukin (IL)-2 is currently used to enhance T-cell immunity but can have both positive and negative effects on T cells. To determine whether these opposing results are due to IL-2 acting differently on T cells depending on their stage of differentiation, we examined the effects of IL-2 therapy during the expansion, contraction and memory phases of the T-cell response in lymphocytic choriomeningitis virus (LCMV)-infected mice. IL-2 treatment during the expansion phase was detrimental to the survival of rapidly dividing effector T cells. In contrast, IL-2 therapy was highly beneficial during the death phase, resulting in increased proliferation and survival of virus-specific T cells. IL-2 treatment also increased proliferation of resting memory T cells in mice that controlled the infection. Virus-specific T cells in chronically infected mice also responded to IL-2 resulting in decreased viral burden. Thus, timing of IL-2 administration and differentiation status of the T cell are critical parameters in designing IL-2 therapies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Immunologic Memory / drug effects
  • Interleukin-2 / pharmacology
  • Interleukin-2 / therapeutic use*
  • Lymphocyte Activation / drug effects
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / therapy*
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology

Substances

  • Interleukin-2