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

Diabetes Res Clin Pract. 1996 Sep;34(1):37-46. doi: 10.1016/s0168-8227(96)01328-9.


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-gamma: IFN-gamma; tumour necrosis factor-alpha: TNF-alpha; interleukin-4: IL-4; interleukin-6: IL-6) in the same specimens. The TCR V beta repertoire was not restricted either in the pancreas or the peripheral lymphocytes of IDDM patients. In contrast, the TCR V alpha 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 TCR alpha revealed the presence of dominant clonality in alpha chains of T cells in the patients. IFN-gamma 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 TCR alpha chain are selectively retained and activated within the pancreas of recent-onset IDDM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Consensus Sequence
  • Cytokines / biosynthesis*
  • DNA Primers
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Gene Expression
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / genetics
  • Interleukin-4 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Lymphocytes / immunology
  • Male
  • Molecular Sequence Data
  • Pancreas / immunology*
  • Polymerase Chain Reaction
  • Receptor-CD3 Complex, Antigen, T-Cell / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis*
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Cytokines
  • DNA Primers
  • Interleukin-6
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Interferon-gamma