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

R Zeng, R Spolski, SE Finkelstein, SK Oh… - The Journal of …, 2005 - rupress.org
R Zeng, R Spolski, SE Finkelstein, SK Oh, PE Kovanen, CS Hinrichs, CA Pise-Masison…
The Journal of experimental medicine, 2005rupress.org
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 (CD44low) 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 …
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 (CD44low) 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.
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