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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

2005; National Academy of Sciences; Volume: 102; Issue: 47 Linguagem: Inglês

10.1073/pnas.0508643102

1091-6490

Anjali J. de Souza, Timothy B. Oriss, Katherine J. O’Malley, Anuradha Ray, Larry Kane,

Macrophage Migration Inhibitory Factor

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.