title: A transgenic TCR directs the development of IL-4+ and PLZF+ innate CD4 T cells.
abstract: MHC class II-expressing thymocytes can efficiently mediate positive selection of CD4 T cells in mice. Thymocyte-selected CD4 (T-CD4) T cells have an innate-like phenotype similar to invariant NKT cells. To investigate the development and function of T-CD4 T cells in-depth, we cloned TCR genes from T-CD4 T cells and generated transgenic mice. Remarkably, positive selection of T-CD4 TCR transgenic (T3) thymocytes occurred more efficiently when MHC class II was expressed by thymocytes than by thymic epithelial cells. Similar to polyclonal T-CD4 T cells and also invariant NKT cells, T3 CD4 T cell development is controlled by signaling lymphocyte activation molecule/signaling lymphocyte activation molecule-associated protein signaling, and the cells expressed both IL-4 and promyelocytic leukemia zinc finger (PLZF). Surprisingly, the selected T3 CD4 T cells were heterogeneous in that only half expressed IL-4 and only half expressed PLZF. IL-4- and PLZF-expressing cells were first found at the double-positive cell stage. Thus, the expression of IL-4 and PLZF seems to be determined by an unidentified event that occurs postselection and is not solely dependent on TCR specificity or the selection process, per se. Taken together, our data show for the first time, to our knowledge, that the TCR specificity regulates but does not determine the development of innate CD4 T cells by thymocytes.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
authors.forename: Lingqiao
authors.initials: L
authors.lastname: Zhu
authors.forename: Yu
authors.initials: Y
authors.lastname: Qiao
authors.forename: Esther S
authors.initials: ES
authors.lastname: Choi
authors.forename: Joy
authors.initials: J
authors.lastname: Das
authors.forename: Derek B
authors.initials: DB
authors.lastname: Sant'angelo
authors.forename: Cheong-Hee
authors.initials: CH
authors.lastname: Chang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D002678:Chimera / Q000235:genetics; D000949:Histocompatibility Antigens Class II; D015847:Interleukin-4 / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D060168:Thymocytes / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics
chemical_list: D015703:Antigens, CD; D000949:Histocompatibility Antigens Class II; D051741:Kruppel-Like Transcription Factors; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D015534:Trans-Activators; C513267:Zbtb16 protein, mouse; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D015847:Interleukin-4