摘要：

Signal inhibitory regulatory proteins are a family of transmembrane glycoproteins involved in the negative regulation of receptor tyrosine kinase signaling pathways. MyD-1 is a recently described member of this family. In this report we have assessed the function of MyD-1 in regulating T cell function utilizing an anti-MyD-1-specific monoclonal antibody (mAb). We show that ligating MyD-1on antigen-presenting cells (APC) inhibits subsequent T cell activation induced by either anti-CD3 mAb or by allogeneic APC but has no effect on responses to either tuberculin purified protein derivative or tetanus toxoid antigens. Moreover, we show that the inhibition of T cell responses is not due to any change of costimulatory molecule expression on APC. We observed that the production of TNFα, a cytokine that we have earlier identified as important in the mechanism of MyD-1 immune regulation, is inhibited by cross-linking of MyD-1. We further show that TNFα is critically important in the regulation of T cell responses in the absence of danger signals, and indeed addition of TNFα can overcome the inhibitory effects of anti-MyD-1 antibody. This information may lead to a betterunderstanding of the regulation of T cell responses in the absence of danger and therefore offer a possible therapeutic target to modulate aberrant immune responses.

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