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

Nature Immunology volume 6, pages 447–454 (2005)Cite this article

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Abstract

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-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.

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Figure 1: Expression of TIM-1 in mouse lymphoid cells and tissues.
Figure 2: TIM-1 expression on activated T cells.
Figure 3: Costimulation of T cells by anti-TIM-1.
Figure 4: Anti-TIM-1 enhances T cell responses in vivo.
Figure 5: Anti-TIM-1 enhances T cell responses of HBA mice.
Figure 6: Anti-TIM-1 inhibits tolerance induction in vivo.
Figure 7: Anti-TIM-1 inhibits tolerance induction in an AHR model.

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Change history

  • 30 March 2005

    Changed a word in the abstract

  • 27 November 2006

    Corrected supp info files uploaded

Notes

  1. NOTE:In the version originally published online, the gene symbol in the first sentence of the abstract was incorrect. The sentence should read as follows: “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.” This error has been corrected for the HTML version of this article online. The correction has been appended to the PDF version online.

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Acknowledgements

We thank G. Kaplan for discussions and B.-G. Zhu for technical assistance. Supported by the National Institutes of Health (PO1 AI54456 to D.T.U., R.D.K. and G.F.; and RO1 HL69507 to R.D.K.).

Author information

Authors and Affiliations

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

    Sarah E Umetsu, Wan-Ling Lee, Jennifer J McIntire, Laura Downey & Bharati Sanjanwala

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

    Omid Akbari, Dale T Umetsu & Rosemarie H DeKruyff

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

    Gerald J Berry

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

    Haruo Nagumo & Gordon J Freeman

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  1. Sarah E Umetsu
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Corresponding author

Correspondence to Rosemarie H DeKruyff.

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Supplementary information

Supplementary Fig. 1

Monoclonal antibody 3B3 is specific for mTIM-1. (PDF 181 kb)

Supplementary Fig. 2

Anti-mTIM-1 mAb 3B3 blocks binding of mTIM-1-Ig to 300.19 cells. (PDF 130 kb)

Supplementary Fig. 3

Monovalent Fab fragments of the anti-TIM-1 mAb bind to TIM-1. (PDF 151 kb)

Supplementary Fig. 4

Anti-Tim1 does not enhance IFN-γ production in TH1 cells at any dose of antigen. (PDF 149 kb)

Supplementary Fig. 5

TIM-1 expression on T cells from HBA mice. (PDF 314 kb)

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Umetsu, S., Lee, WL., McIntire, J. et al. TIM-1 induces T cell activation and inhibits the development of peripheral tolerance. Nat Immunol 6, 447–454 (2005). https://doi.org/10.1038/ni1186

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