The Vitronectin Receptor Serves as an Accessory Molecule for the Activation of a Subset of y/b T Cells

Constitutive production of cytokines was observed in 3 o£ 12 ylb T cell lines derived from murine epidermis and correlated with the expression of the Cy4, V66 T cell receptor (TCR). After adaptation of one of the lines (T195/BW) to serum-free culture conditions, cessation of the "spontaneous" production of interleukin 4 (IJ. 4) was observed and 11=4 production could then be induced by the addition ofRGD-containing extracellular matrix (ECM) proteins to the culture. The response to the ECM proteins could be completely inhibited by a mAb to the murine vitronectin receptor (VNR). However, the induction of IL-4 production could also be inhibited by anti-CD3 and by an anti-clonotypic mAb to the TCR-y/b of T195/BW As TCR-ylb loss mutants of T195/BW also failed to respond to ECM proteins, these data demonstrate that engagement of the VNR by its ligand is necessary, but not sufficient, for the induction of IL4 production. Furthermore, the VNR is expressed by many other T cell clones (both y/b and x//3), none of which produce lymphokines constitutively. Taken together, these observations strongly favor the view that not only is coexpression of the VNR and TCR required for the induction of IL4 production, but that the TCR must also be engaged by its ligand, most likely a cell surface antigen expressed by the hybridoma itself.