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Article
Nature Immunology - 6, 447 - 454 (2005)
Published online: 27 March 2005; Corrected online: 30 March 2005 ; Corrected online: 27 November 2006 | doi:10.1038/ni1186

TIM-1 induces T cell activation and inhibits the development of peripheral tolerance

Sarah E Umetsu1, Wan-Ling Lee1, Jennifer J McIntire1, Laura Downey1, Bharati Sanjanwala1, Omid Akbari2, Gerald J Berry3, Haruo Nagumo4, Gordon J Freeman4, Dale T Umetsu2 & Rosemarie H DeKruyff2

1  Department of Pediatrics, Stanford University, Stanford, California 94305, USA.

2  Division of Immunology, Children's Hospital Boston, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.

3  Department of Pathology, Stanford University, Stanford, California 94305, USA.

4  Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.

Correspondence should be addressed to Rosemarie H DeKruyff rosemarie.dekruyff@childrens.harvard.edu

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 (TH2) but not TH1 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 TH2 cells, such costimulation greatly enhanced synthesis of interleukin 4 but not interferon-bold gamma. In vivo, the use of antibody to TIM-1 plus antigen substantially increased production of both interleukin 4 and interferon-bold 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.
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.

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Nature Immunology
ISSN: 1529-2908
EISSN: 1529-2916
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