Tim-1 signaling substitutes for conventional signal 1 and requires costimulation to induce T cell proliferation

Christophe Mariat, Nicolas Degauque, Savithri Balasubramanian, James Kenny, Rosemarie H. DeKruyff, Dale T. Umetsu, Vijay Kuchroo, Xin Xiao Zheng, Terry B. Strom

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Differentiation and clonal expansion of Ag-activated naive T cells play a pivotal role in the adaptive immune response. T cell Ig mucin (Tim) proteins influence the activation and differentiation of T cells. Tim-3 and Tim-2 clearly regulate Th1 and Th2 responses, respectively, but the precise influence of Tim-1 on T cell activation remains to be determined. We now show that Tim-1 stimulation in vivo and in vitro induces polyclonal activation of T cells despite absence of a conventional TCR-dependent signal 1. In this model, Tim-1-induced proliferation is dependent on strong signal 2 costimulation provided by mature dendritic cells. Ligation of Tim-1 upon CD4+ T cells with an agonist anti-Tim-1 mAb elicits a rise in free cytosolic calcium, calcineurin-dependent nuclear translocation of NF-AT, and transcription of IL-2. Because Tim-4, the Tim-1 ligand, is expressed by mature dendritic cells, we propose that interaction between Tim-1+ T cells and Tim-4+ dendritic cells might ensure optimal stimulation of T cells, when TCR-derived signals originating within an inflamed environment are weak or waning.

Original languageEnglish
Pages (from-to)1379-1385
Number of pages7
JournalJournal of Immunology
Volume182
Issue number3
DOIs
StatePublished - 1 Feb 2009
Externally publishedYes

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