BATF transgenic mice reveal a role for activator protein-1 in NKT cell development.
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.
Williams
Kristi L
KL
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Zullo
Alfred J
AJ
Kaplan
Mark H
MH
Brutkiewicz
Randy R
RR
Deppmann
Christopher D
CD
Vinson
Charles
C
Taparowsky
Elizabeth J
EJ
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology; D050976:Basic-Leucine Zipper Transcription Factors; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D019076:Transgenes / Q000276:immunology
D050976:Basic-Leucine Zipper Transcription Factors; C431772:Batf protein, mouse; D016207:Cytokines; D018808:Transcription Factor AP-1; D014157:Transcription Factors