BATF Transgenic Mice Reveal a Role for Activator Protein-1 in NKT Cell Development

• Published in: The Journal of immunology (1950) 2003-03, Vol.170 (5), p.2417-2426
• Main Authors: Williams, Kristi L, Zullo, Alfred J, Kaplan, Mark H, Brutkiewicz, Randy R, Deppmann, Christopher D, Vinson, Charles, Taparowsky, Elizabeth J
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocyte Subsets - cytology; Basic-Leucine Zipper Transcription Factors; CD4-Positive T-Lymphocytes - immunology; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Division - genetics; Cell Division - immunology; Cells, Cultured; Cytokines - antagonists & inhibitors; Cytokines - biosynthesis; Cytokines - genetics; Humans; Immunophenotyping; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Killer Cells, Natural - pathology; Lymphocyte Activation - genetics; Lymphopenia - genetics; Lymphopenia - immunology; Lymphopenia - pathology; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Mice, Transgenic - genetics; Mice, Transgenic - immunology; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - pathology; Thymus Gland - cytology; Thymus Gland - immunology; Thymus Gland - pathology; Transcription Factor AP-1 - antagonists & inhibitors; Transcription Factor AP-1 - physiology; Transcription Factors - biosynthesis; Transcription Factors - genetics; Transcription Factors - physiology; Transgenes - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.170.5.2417

The importance of regulated AP-1 activity during T cell development was assessed using transgenic mice overexpressing BATF, a basic leucine zipper transcription factor and an AP-1 inhibitor. BATF transgenic animals possess normal thymic cellularity and all major T cell subsets, but show impaired thymocyte proliferation in vitro and no induction of IL-2, IL-4, IL-5, IL-10, and IL-13 expression. Since NKT cells are largely responsible for cytokine production in the thymus, this population was examined by detection of the V alpha 14-J alpha 281 TCR, flow cytometry of NK1.1(+) TCR beta(+) cells, and analysis of cytokine production by heat-stable Ag(low) thymocytes and peripheral NKT cells stimulated in vivo. Results show a severe under-representation of NKT cells in BATF transgenic animals, providing the first evidence that the precise control of AP-1-mediated transcription is critical for the proper emergence of thymus-derived NKT cells in the mouse.