期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 102, 期 47, 页码 17113-17118出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0508643102
关键词
costimulation; phosphorylation; asthma; cytokines
资金
- NIAID NIH HHS [AI 48927, R01 AI048927] Funding Source: Medline
Polymorphisms in TIM-1, a member of the T cell Ig and mucin (TIM) domain family, are associated with relative susceptibility to the development of T helper 2-dominated immune responses such as in allergic asthma. Recent data have also suggested that ligation of TIM-1 can augment T cell activation. We have found that the TIM-1 protein is expressed on CD4(+) T cells in vivo after intranasal immunization. Ectopic expression of TIM-1 during T cell differentiation results in a significant increase in the number of cells producing IL-4 but not IFN-gamma. Furthermore, TIM-1 expression provides a costimulatory signal that increases transcription from the IL-4 promoter and from isolated nuclear factor of activated T cells/activating protein-1 (NFAT/AP-1) elements. Finally, we provide evidence that TIM-1 can be phosphorylated on tyrosine and that TIM-1 costimulation requires its cytoplasmic tail and the conserved tyrosine within that domain. These results constitute evidence that TIM-1 directly couples to phosphotyrosine-dependent intracellular signaling pathways.
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