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Publication : A CD8/Lck transgene is able to drive thymocyte differentiation.

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.
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