Résumé
Thymocytes expressing the NKT cell semi-invariant αβ TCR are thought to undergo agonist interactions with CD1d ligands prior to expressing PLZF, a BTB-POZ transcription factor that directs acquisition of the effector program of these innate-like T cells. Whether PLZF can mediate this effector conversion independently of agonist signaling has not been investigated. We demonstrated that transgenic expression of PLZF under the CD4 promoter induced the innate effector program in two different MHC class II-restricted TCR transgenic Rag1−/− models examined. In CD4 thymocytes expressing a fixed transgenic TCR β chain, the associated TCR α sequences in wild-type and PLZF-transgenic mice overlapped extensively, further demonstrating that PLZF could induce the effector program in most CD4 T cells that would normally be selected as naÔve cells. In contrast, PLZF altered the negative selection of thymocytes expressing TCR β chains reactive against several retroviral superantigens. Thus, PLZF is the first example of a transcription factor inducing an effector program in the absence of T cell agonist interactions or cell division. Its expression may also enhance the survival of agonist-signaled thymocytes.