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. 2003 Nov;4(11):1102-10.
doi: 10.1038/ni988. Epub 2003 Oct 12.

Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance

Catherine A Sabatos  1 , Sumone Chakravarti, Eugene Cha, Anna Schubart, Alberto Sánchez-Fueyo, Xin Xiao Zheng, Anthony J Coyle, Terry B Strom, Gordon J Freeman, Vijay K Kuchroo
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Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance

Catherine A Sabatos et al. Nat Immunol. 2003 Nov.

Abstract

T helper type 1 (T(H)1) immune responses are central in cell-mediated immunity, and a T(H)1-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 T(H)1 cells and T(H)1 cytokine release. Tim-3-Ig also abrogated tolerance induction in T(H)1 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 T(H)1 cells during a normal immune response and may be crucial for the induction of peripheral tolerance.

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