title: Promyelocytic leukemia zinc finger turns on the effector T cell program without requirement for agonist TCR signaling.
abstract: Thymocytes expressing the NKT cell semi-invariant αβ TCR are thought to undergo agonist interactions with CD1d ligands prior to expressing promyelocytic leukemia zinc finger (PLZF), a broad complex, tramtrack, bric-a-brac, poxvirus, and zinc finger 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 (Tg) expression of PLZF under the CD4 promoter induced the innate effector program in two different MHC class II-restricted TCR-Tg Rag1(-/-) models examined. In CD4 thymocytes expressing a fixed Tg TCR β-chain, the associated TCRα sequences in wild-type and PLZF-Tg mice overlapped extensively, further demonstrating that PLZF could induce the effector program in most CD4 T cells that would normally be selected as naive cells. In contrast, PLZF altered the negative selection of thymocytes expressing TCR β-chains reactive against several retroviral superantigens. Thus, PLZF is remarkable in that it is a transcription factor capable of 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.
authors.affiliation: Committee on Immunology, Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Adam K
authors.initials: AK
authors.lastname: Savage
authors.forename: Michael G
authors.initials: MG
authors.lastname: Constantinides
authors.forename: Albert
authors.initials: A
authors.lastname: Bendelac
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D055610:Antigens, CD1d / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011828:Radiation Chimera; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D016335:Zinc Fingers; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D055610:Antigens, CD1d; D000945:Antigens, Differentiation, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D051741:Kruppel-Like Transcription Factors; D037181:Lectins, C-Type; D008024:Ligands; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000099192:CD69 Antigens; C513267:Zbtb16 protein, mouse