title: Dominant TCR alpha-chain clonotypes and interferon-gamma 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-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.
authors.affiliation: Second Department of Internal Medicine, Osaka University Medical School, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamagata
authors.forename: H
authors.initials: H
authors.lastname: Nakajima
authors.forename: K
authors.initials: K
authors.lastname: Tomita
authors.forename: N
authors.initials: N
authors.lastname: Itoh
authors.forename: J
authors.initials: J
authors.lastname: Miyagawa
authors.forename: T
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: M
authors.initials: M
authors.lastname: Namba
authors.forename: S
authors.initials: S
authors.lastname: Tamura
authors.forename: S
authors.initials: S
authors.lastname: Kawata
authors.forename: N
authors.initials: N
authors.lastname: Kono
authors.forename: M
authors.initials: M
authors.lastname: Kuwajima
authors.forename: T
authors.initials: T
authors.lastname: Noguchi
authors.forename: T
authors.initials: T
authors.lastname: Hanafusa
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D016384:Consensus Sequence; D016207:Cytokines / Q000096:biosynthesis*; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D010179:Pancreas / Q000276:immunology*; D016133:Polymerase Chain Reaction; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D017931:DNA Primers; D015850:Interleukin-6; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma