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TIM-1 induces T cell activation and inhibits the development of peripheral tolerance
TIM-1 induces T cell activation and inhibits the development of peripheral tolerance NATURE IMMUNOLOGY Umetsu, S. E., Lee, W. L., McIntire, J. J., Downey, L., Sanjanwala, B., Akbari, O., Berry, G. J., Nagumo, H., Freeman, G. J., Umetsu, D. T., DeKruyff, R. H. 2005; 6 (5): 447-454Abstract
We have examined the function of TIM-1, encoded by a gene identified as an 'atopy susceptibility gene' (Havcr1*), and demonstrate here that TIM-1 is a molecule that costimulates T cell activation. TIM-1 was expressed on CD4(+) T cells after activation and its expression was sustained preferentially in T helper type 2 (T(H)2) but not T(H)1 cells. In vitro stimulation of CD4(+) T cells with a TIM-1-specific monoclonal antibody and T cell receptor ligation enhanced T cell proliferation; in T(H)2 cells, such costimulation greatly enhanced synthesis of interleukin 4 but not interferon-gamma. In vivo, the use of antibody to TIM-1 plus antigen substantially increased production of both interleukin 4 and interferon-gamma in unpolarized T cells, prevented the development of respiratory tolerance, and increased pulmonary inflammation. Our studies suggest that immunotherapies that regulate TIM-1 function may downmodulate allergic inflammatory diseases.
View details for DOI 10.1038/ni1186
View details for PubMedID 15793575