Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance
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- 12 October 2003
- journal article
- research article
- Published by Springer Nature in Nature Immunology
- Vol. 4 (11) , 1102-1110
- https://doi.org/10.1038/ni988
Abstract
T helper type 1 (TH1) immune responses are central in cell-mediated immunity, and a TH1-specific cell surface molecule called Tim-3 (T cell immunoglobulin domain, mucin domain) has been identified. Here we report the identification of a secreted form of Tim-3 that contains only the immunoglobulin (Ig) variable (V) domain of the full-length molecule. Fusion proteins (Tim-3–Ig) of both Tim-3 isoforms specifically bound CD4+ T cells, indicating that a Tim-3 ligand is expressed on CD4+ T cells. Administration of Tim-3–Ig to immunized mice caused hyperproliferation of TH1 cells and TH1 cytokine release. Tim-3–Ig also abrogated tolerance induction in TH1 cells, and Tim-3-deficient mice were refractory to the induction of high-dose tolerance. These data indicate that interaction of Tim-3 with Tim-3 ligand may serve to inhibit effector TH1 cells during a normal immune response and may be crucial for the induction of peripheral tolerance.Keywords
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