EPITOPE SPECIFICITY, CYTOKINE PRODUCTION PROFILE AND DIABETOGENIC ACTIVITY OF INSULIN-SPECIFIC T-CELL CLONES ISOLATED FROM NOD MICE

T cells are known to play an important role in beta cell destruction i n the nonobese diabetic (NOD) mouse model of Type I diabetes and islet -specific T cell clones have been demonstrated to be capable of adopti ve transfer of diabetes. One important issue involves the identity of beta cell antigens that are recognized by nominally islet cell-specifi c T cell clones. We have previously reported that insulin-specific T c ells are a predominant component of islet-specific T cells isolated fr om islet infiltrates of pre-diabetic NOD mice. In this report we exami ne six independently derived insulin-specific T cell clones establishe d from islet infiltrates of pre-diabetic NOD mice in detail. All six c lones were found to be specific to a region of the insulin molecule de fined by a synthetic peptide encompassing residues 9-23 of the B chain . Despite this restricted specificity, each member of this panel exhib ited 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 c haracteristic of THO cells. All six clones were capable of either acce leration of diabetes in young NOD mice or adoptive transfer to NODscid mice. Taken together, these results suggest that spontaneously arisin g insulin-specific T cells participate in beta cell destruction during development of diabetes in NOD mice.