Influence of cytokines and TLR agonists on CD49a, CD49b and CD103 expression by T cells (CAM4P.152)

Abstract

Abstract Integrins CD49a (alpha1), CD49b (alpha2) and CD103 (alphaE) are highly expressed on tumor infiltrating lymphocytes (TILs) compared to circulating lymphocytes. Interactions of the integrins with known ligands support retention of lymphocytes in peripheral tissues; thus, they may be considered retention integrins (RI). T cells in peripheral tissues expressing RI have a cytotoxic phenotype and RI+ TIL are associated with improved patient survival. Despite their importance in retention of tumor reactive TILs, little is known about pathways inducing RI expression, except that TGFβ induces CD103. We hypothesized that other cytokines, TLR agonists, and T cell receptor (TCR) stimulation can induce RI expression by circulating T cells. We stimulated PBMC with cytokines or TLR agonists after TCR stimulation, and evaluated RI expression by flow cytometry after 2-7 days. Both CD103 and CD49a are induced by TGFβ, most strikingly on activated T cells. IL2 and IL10 also influence CD49a expression. CD49b expression is increased by IL2, IL4 and IL10, although this depends on T cell subset and activation state. TLR2, TLR6 and TLR7 agonists also appear to induce CD49a and CD49b. In conclusion, our results support our hypothesis by showing that RI expression is tightly regulated by cytokine and TCR stimulation. Furthermore these regulating factors have different effects among the RI, suggesting a different role for each.