| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Despite a large number of T cells infiltrating into the liver of patients with autoimmune hepalitis (AIH), little is known about their roles or target antigens. To investigate the roles of these T cells in the pathogenesis of AIR, l) we have studied the clonality of alphabeta T cell populations. in liver tissue by size spectratyping the complementarity-determining region (CDR)3 size lengths of T cell receptor (TCR) Vbeta-chain transcripts and 2) we have tryed to induce asialoglycoprotein receptor antigen (ASGPR)-specific T cells.
1) T cells infiltrating into the liver.
Analysis of ten patients with AIH, who all had the HLA DR4 haplotype, showed clonal expansion in nine liver. More than two T cell clones expanded in most patients. Although the expression of the TCR Vbeta genes was different among the nine patients, clonal expansion of T cells expressing either TCR Vbeta2, 3, 4, 16 or 22 were observed in two patients or more. TCR Vbeta4 clones expanded in 5 cases. Cloning and sequencing of TCR Vbeta CDR3 from PCR products revealed no whole CDR3-shared clones among different patients. In conclusion, a diverse set of T cell clonotypes first recognize target antigens, then expand and accumulate in the liver of AIR patients. These suggest the heterogeneity of autoantigens and the complexity of AIH immunopathogenesis.
2) ASGPR-specific T cells
Periferal blood lymphocytes (PBL) from AIH, chronic hepatitis (CR)-B and -C, primary biliary cirrhosis patients and healthy control were stimulated by ASGPR.T cells of not only AIH but CH-C patients proliferated but those of others did not. It is likely that ASGPR is one of antigen recognized by T cells of AIH and CR-C patients.
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