Epitope specificity, cytokine production profile and diabetogenic activity of insulin-specific T cell clones isolated from NOD mice

European Journal of Immunology
D DanielD Wegmann

Abstract

T cells are known to play an important role in beta cell destruction in the nonobese diabetic (NOD) mouse model of Type I diabetes and islet-specific T cell clones have been demonstrated to be capable of adoptive transfer of diabetes. One important issue involves the identity of beta cell antigens that are recognized by nominally islet cell-specific T cell clones. We have previously reported that insulin-specific T cells are a predominant component of islet-specific T cells isolated from islet infiltrates of pre-diabetic NOD mice. In this report we examine six independently derived insulin-specific T cell clones established from islet infiltrates of pre-diabetic NOD mice in detail. All six clones were found to be specific to a region of the insulin molecule defined by a synthetic peptide encompassing residues 9-23 of the B chain. Despite this restricted specificity, each member of this panel exhibited a distinct receptor specificity defined either by V beta usage or antigen fine specificity. Five clones produced interferon (IFN)-gamma but not interleukin (IL)-4, placing them in the T helper type 1 (TH1)-like category whereas one clone produced both IL-4 and IFN-gamma, a characteristic of TH0 cells. All six clones were capable o...Continue Reading

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