DOMINANT TCR ALPHA-CHAIN CLONOTYPES AND INTERFERON-GAMMA ARE EXPRESSED IN THE PANCREAS OF PATIENTS WITH RECENT-ONSET INSULIN-DEPENDENT DIABETES-MELLITUS

In order to clarify the nature of T lymphocytes infiltrating the pancr eatic islets of patients with insulin-dependent diabetes mellitus (IDD M), we analysed T cell receptor (TCR) gene transcripts expressed in pa ncreatic biopsy specimens of patients with recent-onset IDDM. We also investigated the expression of cytokines (interferon-gamma: IFN-gamma; tumour necrosis factor-alpha: TNF-alpha; interleukin-4: IL-4; interle ukin-6: IL-6) in the same specimens. The TCR V beta repertoire was not restricted either in the pancreas or the peripheral lymphocytes of ID DM patients. In contrast, the TCR V alpha repertoire was restricted in the pancreas, but not in the peripheral blood lymphocytes, of IDDM pa tients. The sequence analysis of the complementarity-determining regio n 3 (CDR3) of the TCR alpha revealed the presence of dominant clonalit y in alpha chains of T cells in the patients. IFN-gamma mRNA was highl y expressed in the pancreas of IDDM patients, while IL-4 mRNA was defi cient. A lower level of expression of IL-6 mRNA was detected in the ID DM pancreas than in the control tissue. These results indicate that T cells bearing a distinct TCR alpha chain are selectively retained and activated within the pancreas of recent-onset IDDM.