Evidence against epitope spreading of T cells in autoimmune diseases.

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Epitope spreading is a well known phenomenon of autoimrnune process especially in the induction phase of the diseases. We examine whether this phenomenon is also working in the stage of advanced phase of autoimmune disorders. We have examined accumulated T cells clones in the several organs of spontaneous models of autoimmune disorders by RT PCR/SSCP analysis of T cell receptor. We found that there are extensive accumulations of T cells in the lesions of late phase animals and the same clones exist in the different pathological lesions of kidney, lung and central nervous system of such animals. We then constructed cDNA library from a single cell isolated from the lesions and obtained fill length cDNAs encoding alpha and beta chains of T cell receptor. After identification of the in vivo accumulated clones to the cloned T cell receptors, cytokine messages were examined using the cDNA library. Some clones were found to express interferon gamma message, suggesting that such clones were pathogenic T cells. We are now trying to reconstitute T cell receptor function by retroviral gene transfer in order to know the pathogenic properties of such clones.