First Author | Fragoso RC | Year | 2006 |
Journal | J Immunol | Volume | 177 |
Issue | 9 | Pages | 6007-17 |
PubMed ID | 17056525 | Mgi Jnum | J:140528 |
Mgi Id | MGI:3814029 | Doi | 10.4049/jimmunol.177.9.6007 |
Citation | Fragoso RC, et al. (2006) A CD8/Lck transgene is able to drive thymocyte differentiation. J Immunol 177(9):6007-17 |
abstractText | 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 CD8alpha-associated Lck in driving CD8 single positive (SP) thymocyte development. We used a chimeric molecule encoding the extracellular and transmembrane domains of CD8alpha fused to full-length Lck. In mice deficient for CD8alpha 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 CD8alpha. A CD8alpha/Lck kinase-dead chimera also resulted in reconstitution of CD8 SP thymocytes. Our results suggest that CD8alpha-associated Lck is sufficient to drive CD8 SP thymocyte development. Furthermore, this CD8 SP development may not necessarily depend on Lck kinase activity. |