Therapeutic use of IL-2 to enhance antiviral T-cell responses in vivo

Joseph N. Blattman, Jason M. Grayson, E. John Wherry, Susan M. Kaech, Kendall A. Smith, Rafi Ahmed

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270 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)540-547
Number of pages8
JournalNature Medicine
Volume9
Issue number5
DOIs
StatePublished - May 1 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Blattman, J. N., Grayson, J. M., Wherry, E. J., Kaech, S. M., Smith, K. A., & Ahmed, R. (2003). Therapeutic use of IL-2 to enhance antiviral T-cell responses in vivo. Nature Medicine, 9(5), 540-547. https://doi.org/10.1038/nm866