Abstract
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.
Publication types
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
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
Substances
-
Basic-Leucine Zipper Transcription Factors
-
Batf protein, mouse
-
Cytokines
-
Transcription Factor AP-1
-
Transcription Factors