Dominant TCR α-chain clonotypes and interferon-γ are expressed in the pancreas of patients with recent-onset insulin-dependent diabetes mellitus

Abstract

In order to clarify the nature of T lymphocytes infiltrating the pancreatic islets of patients with insulin-dependent diabetes mellitus (IDDM), we analysed T cell receptor (TCR) gene transcripts expressed in pancreatic biopsy specimens of patients with recent-onset IDDM. We also investigated the expression of cytokines (interferon-γ: IFN-γ; tumour necrosis factor-α: TNF-α; interleukin-4: IL-4; interleukin-6: IL-6) in the same specimens. The TCR Vβ repertoire was not restricted either in the pancreas or the peripheral lymphocytes of IDDM patients. In contrast, the TCR Vα repertoire was restricted in the pancreas, but not in the peripheral blood lymphocytes, of IDDM patients. The sequence analysis of the complementarity-determining region 3 (CDR3) of the TCRα revealed the presence of dominant clonality in α chains of T cells in the patients. IFN-γ mRNA was highly expressed in the pancreas of IDDM patients, while IL-4 mRNA was deficient. A lower level of expression of IL-6 mRNA was detected in the IDDM pancreas than in the control tissue. These results indicate that T cells bearing a distinct TCRα chain are selectively retained and activated within the pancreas of recent-onset IDDM.