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The Journal of Immunology, 2003, 170: 2417-2426.
Copyright © 2003 by The American Association of Immunologists

BATF Transgenic Mice Reveal a Role for Activator Protein-1 in NKT Cell Development1

Kristi L. Williams*, Alfred J. Zullo*, Mark H. Kaplan{dagger}, Randy R. Brutkiewicz{dagger}, Christopher D. Deppmann*, Charles Vinson{ddagger} and Elizabeth J. Taparowsky2,*

* Department of Biological Sciences, Purdue University, West Lafayette, IN 47907; {dagger} Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202; and {ddagger} Laboratory of Biochemistry, National Institutes of Health, Bethesda, MD 20892

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 Aglow 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.




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