REGULATION OF CD2-MEDIATED HETEROTYPIC INTERACTIONS OF MURINE T-LYMPHOCYTES

In this study we have investigated the expression and function of the murine CD2 receptor in T cells. The surface level of CD2 increased bet ween 300 and 400% when T cells were activated, which also induced a ra pid increase of nearly 40-fold in the steady-state levels of CD2 mRNA. Although the activated lymphocytes were found to internalize and degr ade nearly 50% of membrane-bound CD2, in addition to shedding the CD2 receptor from the cell surface, this does not account for the discrepa ncy between the increase in mRNA and antigen levels during activation. These findings suggest that the expression of CD2 is also regulated b y post-transcriptional processes which control the translational effic iency of the CD2 message. Activation of T cells enhanced their interac tion with mesenchymal cell targets (fibroblasts) via a CD2-dependent a dhesion pathway which was not inhibited by the anti-mouse CD48 (sgp-60 ) mAb OX78, the only counter-receptor thus far identified on other cel ls as a ligand for the mouse CD2 receptor. Moreover, since murine fibr oblasts were found not to express CD48, our results implicate a novel ligand for CD2, possibly a homologue of the human LFA-3. This new path way of heterotypic T cell interaction would be facilitated by utilizat ion of the large intracellular pool of CD2 transcripts to up-regulate CD2 expression and, as this receptor is a major signal-transducing mol ecule, would further enhance T cell activation and increase CD2-mediat ed adhesion. (C) 1994 Academic Press, Inc.