FADD/MORT1 regulates the pre-TCR checkpoint and can function as a tumour suppressor

Abstract

Productive rearrangement of the T-cell receptor (TCR) β gene and signalling through the pre-TCR-CD3 complex are required for survival, proliferation and differentiation of T-cell progenitors (pro-T cells). Here we identify a role for death receptor signalling in early T-cell development using a dominant-negative mutant of the death receptor signal transducer FADD/MORT1 (FADD-DN). In rag-1(-/-) thymocytes, which are defective in antigen receptor gene rearrangement, FADD-DN bypassed the requirement for pre-TCR signalling, promoting pro-T-cell survival and differentiation to the more mature pre-T stage. Surprisingly, differentiation was not accompanied by the proliferation that occurs normally ..