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_H2) but not T_H1 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_H2 cells, such costimulation greatly enhanced synthesis of interleukin 4 but not interferon-γ. In vivo, the use of antibody to TIM-1 plus antigen substantially increased production of both interleukin 4 and interferon-γ 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.

NOTE: In the supplementary information initially published online to accompany this article, the legends for the supplementary figures are attached to the wrong figures. The error has been corrected online.