Stat6 signaling suppresses VLA-4 expression by CD8+ T cells and limits their ability to infiltrate tumor lesions in vivo

Kotaro Sasaki, Xi Zhao, Angela D. Pardee, Ryo Ueda, Mitsugu Fujita, Sarita Sehra, Mark H. Kaplan, Lawrence P. Kane, Hideho Okada, Walter J. Storkus

研究成果: Article査読

24 被引用数 (Scopus)


VLA-4 plays a critical role in T cell trafficking into inflammatory sites. Our recent studies have suggested that VLA-4 expression on CD8+ T cells is negatively controlled by IL-4 and serves as a functionally distinguishing variable for why Type-1, but not Type-2, CD8+ T cells are able to traffic into tumors. In this study, using in vitro culture of murine CD8+ T cells under Type-1 and Type-2 cytokine conditions, we show that IL-4-mediated down-regulation of VLA-4 expression is completely abrogated in Stat6-deficient CD8+ T cells. Conversely, CD8+ T cells expressing a constitutively active mutant form Stat6 (Stat6VT) failed to express VLA-4 even in the absence of IL-4-stimuIation. Notably, Type-2 CD8+ T cells developed from Stat6-/- but not wild-type mice were competent to migrate into tumor lesions in vivo. These results suggest that Stat6-signaling is necessary and sufficient to restrict CD8+ T cell expression of VLA-4 (by IL-4), thereby serving as a regulator for CD8 + T cell infiltration into tumors.

ジャーナルJournal of Immunology
出版ステータスPublished - 2008

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学


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