| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
The initial cellular events that take place at the outset of autoimmune diseases and which may be the most important in terms of understanding their pathogenesis are poorly understood, especially in humans. This is mainly due to the difficulties in the identification of primary lesions and the accessibility to such material. In this respect, it is noteworthy that the appearance of small reddish erosions, known as aphthoid lesions, is known to be an early event in Crohn's disease. In the present study, accumulation of lesion-specific clonal T-cell receptor bands in the intestinal lesions of Crohn's disease patients was demonstrated by means of a highly sensitive method based on single strand conformational polymorphism. Such clonal accumulation was demonstrated in both aphthoid and discrete ulcer lesions. The number of the early lesion-specific/dominant TCR clones was no more than 7 in one patient. There were several TCRBV bands that were present in both aphthoid lesions and discrete ulcer lesions, but some were specific to the aphthoid lesions. In addition, the same aphthoid lesion-specific/dominant T cell clones were found to be expanded in separate aphthoid lesions of a single patient, and were absent from intervening, non-inflamed mucosa. The BV segments that displayd aphthoid lesion-specific oligoclonality were quite diverse and showed no obvious pattern. This argues against a role for superantigens in the pathogenesis of CD.Furthermore, there was no obvious relationship between the BV segments that displayd aphthoid lesion-specific oligoclonality and the HLA type of the individual. Some of these bands may represent T cell clones activated primarily at the onset of disease.
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