1. Constitutive expression of CIITA directs CD4 T cells to produce Th2 cytokines in the thymus
- Author
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Cheong Hee Chang, Dipak R. Patel, M. Hanief Sofi, Mark H. Kaplan, Tania S. Gourley, Jae Seung Park, Gaio Hangoc, and Wei Li
- Subjects
CD4-Positive T-Lymphocytes ,T-Lymphocytes ,Transgene ,medicine.medical_treatment ,T cell ,Immunology ,Mice, Inbred Strains ,Mice, Transgenic ,chemical and pharmacologic phenomena ,Thymus Gland ,CD8-Positive T-Lymphocytes ,Biology ,Interferon-gamma ,Mice ,Th2 Cells ,CIITA ,medicine ,Animals ,Humans ,Cytotoxic T cell ,Interleukin 4 ,Bone Marrow Transplantation ,STAT6 ,Mice, Knockout ,Interleukins ,Histocompatibility Antigens Class II ,Nuclear Proteins ,Cell Differentiation ,Th1 Cells ,Adoptive Transfer ,Cell biology ,Immunoglobulin Isotypes ,Killer Cells, Natural ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Cytokine ,Trans-Activators ,Cancer research ,Cytokines ,Interleukin-4 ,Bone marrow ,STAT6 Transcription Factor ,Cell Division ,Spleen - Abstract
We generated mice expressing a human type III CIITA transgene (CIITA Tg) under control of the CD4 promoter to study the role of CIITA in CD4 T cell biology. The transgene is expressed in peripheral CD4 and CD8 T cells, as well as in thymocytes. When CD4 T cells were differentiated towards the Th2 lineage, both control and CIITA Tg Th2 cells expressed similar levels of Th2 cytokines. Th1 cells from control and CIITA Tg mice cells produced comparable levels of IFN-γ. CIITA Tg Th1 cells also expressed IL-4, IL-5, and IL-13 in the absence of Stat6. There was an approximate 10-fold increase in the number of peripheral naive CD4 T cells and NK1.1− thymocytes producing IL-4 from CIITA Tg mice compared to control mice. Finally, Th1 cells from irradiated control mice reconstituted with CIITA Tg bone marrow displayed the same cytokine production profiles as Th1 cells from CIITA Tg mice. Together, our data demonstrate that CIITA expression pre-disposes CD4 T cells to produce Th2 type cytokines. Moreover, phenotypic similarities between Th1 cells expressing the CIITA transgene and CIITA deficient Th1 cells suggest that the role of CIITA in cytokine regulation is complex and may reflect both direct and indirect mechanisms of T cell development and differentiation.
- Published
- 2005
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