International Immunology, Vol. 11, No. 6, 957-966,
June 1999
© 1999 Japanese Society for Immunology
Regulation of NOD mouse autoimmune diabetes by T cells that recognize a TCR CDR3 peptide
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
1 Department of Genetics, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
2 Department of Biochemistry, Imperial College of Science, Technology and Medicine, London SW7 2AZ, UK
Correspondence to: I. R. Cohen
NOD mice spontaneously develop type I diabetes resulting from autoimmune destruction of their insulin-producing ß cells. Among the self-antigens targeted by NOD autoimmune T cells is a peptide, p277, from the sequence of the 60 kDa heat shock protein (hsp60). Common to the anti-p277 T cell populations of NOD mice is an idiotope, C9, that spans the CDR3 region of the C9 TCR. We now report: (i) that the C9 idiotope peptide can be presented directly to anti-C9 anti-idiotypic T cells by C9 T cells, (ii) that spontaneous anti-C9 anti-idiotypic T cell activity falls as disease progresses, but immunization can activate the anti-idiotypic T cells to regulate the autoimmune process, (iii) that the anti-idiotypic T cells secrete IFN-
, but appear to control the disease by down-regulating the IFN- produced by the pathogenic population of anti-p277 T cells, (iv) that intrathymic administration of the C9 idiotope peptide at 1 week of age can accelerate the disease, and (v) that administering the p277 target peptide can up-regulate the anti-idiotypic T cells and arrest the disease process. Thus, the development of NOD diabetes can be regulated by a balance between anti-idiotypic and anti-target peptide autoimmunity, and anti-idiotypic regulation can lead to changes in the cytokine secretion of the autoimmune T cells involved in the disease process.
Keywords: anti-idiotypic regulation, autoimmunity, IFN-, type I diabetes
Transmitting editor: L. Steinman
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