CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity

Recent data indicate that the cell surface glycoprotein CD5 functions as a negative regulator of T cell receptor (TCR)-mediated signaling. In this stu dy, we examined the regulation of CD5 surface expression during normal thym ocyte ontogeny and in mice with developmental and/or signal transduction de fects. The results demonstrate that low level expression of CDS on CD4(-)CD 8(-) (double negative, DN) thymocytes is independent of TCR gene rearrangem ent; however, induction of CD5 surface expression on DN thymocytes requires engagement of the pre-TCR and is dependent upon the activity of p56(lck). At the CD4(+)CD8(+) (double positive, DP) stage, intermediate CD5 levels ar e maintained by low affinity TCR-major histocompatibility complex (MHC) int eractions, and. CD5 surface expression is proportional to both the surface level and signaling capacity of the TCR. High-level expression of CD5 on DP and CD4(+) or CD8(+) (single positive, SP) thymocytes is induced by engage ment of the alpha/beta-TCR by (positively or negatively) selecting ligands. Significantly, CD5 surface expression on mature SP thymocytes and T cells was found to directly parallel the avidity or signaling intensity of the po sitively selecting TCR-MHC-ligand interaction. Taken together, these observ ations suggest that the developmental regulation of CD5 in response to TCR signaling and TCR avidity represents a mechanism for tine tuning of the TCR signaling response.