Shared TCR Vbeta gene expression by the pancreas and salivary gland in immunodeficient alymphoplasic mice

Mice with the homozygous mutation alymphoplasia (aly) lack lymph nodes and Peyer's patches and show defects in both humoral and cellular immunity. In these mice, spontaneous infiltration of mononuclear cells was observed in multiple exocrine organs, including the pancreas, salivary glands, and lacrimal glands from the age of 15 wk, progressing to a marked tissue destruction at the age of 25 wk. Using this strain, we examined the phenotypes and TCR Vbeta gene expression of infiltrating T cells to identify the pathologic role of T cell immunity in idiopathic pancreatitis. Most of the infiltrating cells were CD4+ and Thy-1+ cells. Analysis of the TCR gene expression on T cells infiltrating the pancreas and salivary glands showed a high expression of Vbeta1 and Vbeta5 in both organs at the age of 15 wk. In contrast, a diverse expression of TCR Vbeta genes was noted at 25 wk. Sequence analysis of complementarity-determining region 3 (CDR3) of the most prominent TCR Vbeta gene family expressed in these cells, Vbeta1, showed oligoclonal expansion of infiltrating T cells in both organs. Frequent use of glutamine and proline at position 97 was observed in paired tissues. Our data suggest that oligoclonal expansion of organ specific T cells might be one of the etiologic mechanisms of chronic pancreatitis and that common autoantigens could trigger autoimmunity in multiple organs.