IL-21 synergizes with IL-7 to augment expansion and anti-tumor function of cytotoxic T cells

Shujuan Liu, Gregory Lizée, Yanyan Lou, Chengwen Liu, Willem W. Overwijk, Gang Wang, Patrick Hwu

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

IL-21, a recently identified member of the common γ-chain (γc) receptor cytokine family, has been shown to be an important regulator of both innate and adaptive immune responses. In this study, we investigated whether IL-21 could synergize with another γc cytokine, IL-7, to induce enhanced proliferation and effector function of tumor antigen-specific CD8+ T cells. Our results showed that IL-21 could significantly augment the IL-7-induced expansion of cytotoxic T cells, possibly by preventing the cytokine-induced down-regulation of the IL-7Rα (CD127) on antigen-stimulated T cells. IL-21 also greatly enhanced the production of Th1 and inflammatory cytokines by activated T cells, including IFN-γ, IL-2, tumor necrosis factor-α, granulocyte macrophage colony-stimulating factor, IL-1β and IL-6. Finally, the addition of IL-21 to IL-7-cultured CTLs resulted in a considerably higher level of cytolytic activity, as measured by specific killing of tumor cells or antigen-pulsed target cells. These results suggest that IL-21 may play a cooperative role with IL-7 in modulating primary CD8+ T-cell responses and may have important implications for immunotherapy of cancer.

Original languageEnglish (US)
Pages (from-to)1213-1221
Number of pages9
JournalInternational Immunology
Volume19
Issue number10
DOIs
StatePublished - Oct 2007
Externally publishedYes

Fingerprint

Interleukin-7
T-Lymphocytes
Neoplasms
Interleukin-7 Receptor alpha Subunit
Cytokines
Cytokine Receptors
Macrophage Colony-Stimulating Factor
Adaptive Immunity
Neoplasm Antigens
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-1
Innate Immunity
Immunotherapy
Interleukin-2
interleukin-21
Interleukin-6
Down-Regulation
Tumor Necrosis Factor-alpha
Antigens

Keywords

  • Cytotoxic T cell
  • IL-21
  • IL-7
  • Immunotherapy
  • Tumor immunology

ASJC Scopus subject areas

  • Immunology

Cite this

IL-21 synergizes with IL-7 to augment expansion and anti-tumor function of cytotoxic T cells. / Liu, Shujuan; Lizée, Gregory; Lou, Yanyan; Liu, Chengwen; Overwijk, Willem W.; Wang, Gang; Hwu, Patrick.

In: International Immunology, Vol. 19, No. 10, 10.2007, p. 1213-1221.

Research output: Contribution to journalArticle

Liu, Shujuan ; Lizée, Gregory ; Lou, Yanyan ; Liu, Chengwen ; Overwijk, Willem W. ; Wang, Gang ; Hwu, Patrick. / IL-21 synergizes with IL-7 to augment expansion and anti-tumor function of cytotoxic T cells. In: International Immunology. 2007 ; Vol. 19, No. 10. pp. 1213-1221.
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