A CD8/Lck transgene is able to drive thymocyte differentiation

Efficient development of thymocytes requires participation of a CD8 or CD4 coreceptor in the TCR:MHC interaction. Both CD8 and CD4 coreceptor cytoplasmic domains associate with Lck. In this study, we attempted to delineate the role of CD8α-associated Lck in driving CDS single positive (SP) thymocyte development We used a chimeric molecule encoding the extracellular and transmembrane domains of CD8α fused to full-length Lck. In mice deficient for CD8α and transgenic for 2C, a MHC class I-restricted TCR, robust reconstitution of CD8 SP thymocytes occurred both centrally and peripherally. The reconstituted CD8 SP population was phenotypically and functionally comparable to 2C wild-type counterparts expressing endogenous CD8α. A CD8α/Lck kinase-dead chimera also resulted in reconstitution of CDS SP thymocytes. Our results suggest that CD8α-associated Lck is sufficient to drive CD8 SP thymocyte development. Furthermore, this CDS SP development may not necessarily depend on Lck kinase activity.