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Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17113-8. Epub 2005 Nov 11.

T cell Ig and mucin 1 (TIM-1) is expressed on in vivo-activated T cells and provides a costimulatory signal for T cell activation.

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  • 1Department of Immunology and Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.


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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