Restricting Zap70 expression to CD4+CD8+ thymocytes reveals a T cell receptor-dependent proofreading mechanism controlling the completion of positive selection.

ABSTRACT: Although T cell receptor (TCR) signals are essential for intrathymic T cell-positive selection, it remains controversial whether they only serve to initiate this process, or whether they are required throughout to promote thymocyte differentiation and survival. To address this issue, we have devised a novel approach to interfere with thymocyte TCR signaling in a developmental stage-specific manner in vivo. We have reconstituted mice deficient for Zap70, a tyrosine kinase required for TCR signaling and normally expressed throughout T cell development, with a Zap70 transgene driven by the adenosine deaminase (ADA) gene enhancer, which is active in CD4(+)CD8(+) thymocytes but inactive in CD4(+) or CD8(+) single-positive (SP) thymocytes. In such mice, termination of Zap70 expression impaired T

SUBMITTER: Liu X 

PROVIDER: S-EPMC2193832 | biostudies-literature | 2003 Feb

REPOSITORIES: biostudies-literature