Overlapping and asymmetric functions of TCR signaling during thymic selection of CD4 and CD8 lineages.

ABSTRACT: TCR signaling plays a central role in directing developmental fates of thymocytes. Current models suggest TCR signal duration directs CD4 versus CD8 lineage development. To investigate the role of TCR signaling during positive selection directly, we switched signaling off in a cohort of selecting thymocytes and followed, in time, their subsequent fate. We did this using an inducible Zap70 transgenic mouse model that allowed Zap70-dependent signaling to be turned on and then off again. Surprisingly, loss of TCR signaling in CD4(+)CD8(lo) thymocytes did not prevent their development into committed CD4 single positives (SPs), nor their continued maturation to HSA(lo) SPs. However, numbers of CD4 SPs underwent a substantial decline following loss of Zap70 expression, suggesting an essential su

SUBMITTER: Sinclair C 

PROVIDER: S-EPMC4028205 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature