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.
ASJC Scopus subject areas
- Immunology and Allergy