Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function

Rong Zeng, Rosanne Spolski, Steven E. Finkelstein, Sang Kon Oh, Panu E. Kovanen, Christian S. Hinrichs, Cynthia A. Pise-Masison, Michael F. Radonovich, John N. Brady, Nicholas P. Restifo, Jay A. Berzofsky, Warren J. Leonard

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515 Scopus citations


Interleukin (IL)-21 is the most recently recognized of the cytokines that share the common cytokine receptor γ chain [γc], which is mutated in humans with X-linked severe combined immunodeficiency. We now report that IL-21 synergistically acts with IL-15 to potently promote the proliferation of both memory (CD44high) and naive (CD44 low) phenotype CD8+ T cells and augment interferon-γ production in vitro. IL-21 also cooperated, albeit more weakly, with IL-7, but not with IL-2. Correspondingly, the expansion and cytotoxicity of CD8 + T cells were impaired in IL-21R-/- mice. Moreover, in vivo administration of IL-21 in combination with IL-15 boosted antigen-specific CD8+ T cell numbers and resulted in a cooperative effect on tumor regression, with apparent cures of large, established B16 melanomas. Thus, our studies reveal that IL-21 potently regulates CD8+ T cell expansion and effector function, primarily in a synergistic context with IL-15.

Original languageEnglish (US)
Pages (from-to)139-148
Number of pages10
JournalJournal of Experimental Medicine
Issue number1
StatePublished - Jan 3 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Zeng, R., Spolski, R., Finkelstein, S. E., Oh, S. K., Kovanen, P. E., Hinrichs, C. S., Pise-Masison, C. A., Radonovich, M. F., Brady, J. N., Restifo, N. P., Berzofsky, J. A., & Leonard, W. J. (2005). Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function. Journal of Experimental Medicine, 201(1), 139-148.