A ROLE FOR THE ORPHAN STEROID-RECEPTOR NUR77 IN APOPTOSIS ACCOMPANYING ANTIGEN-INDUCED NEGATIVE SELECTION

The transcription factor Nur77, an orphan member of the nuclear hormon e receptor superfamily, is highly expressed during T cell receptor-sig naled apoptosis, suggesting a possible role for Nur77 in negative sele ction. We examined this by generating two sets of transgenic mice, In one set of mice, a dominant-negative Nur77 mutant is constitutively ex pressed and the other in which wild-type Nur77 protein is constitutive ly expressed in developing thymocytes. We report that inhibition of en dogenous Nur77 by the dominant-negative mutant perturbed T cell develo pment and inhibited antigen-induced negative selection in F5 T cell re ceptor transgenic mice, Constitutive expression of wild-type Nur77 pro tein induced apoptosis in developing thymocytes, resulting in a decrea sed number of thymocytes and mature T cells. Together, these data supp ort a role for Nur77 in the downstream signaling events in antigen-ind uced negative selection.