title: Insulin-secretory-granule specific T cell clones in human IDDM.
abstract: T cell clones reactive to beta-cell antigens prepared from different species were established in order to identify putative pathogenic T cells in human IDDM. We were able to generate T cell clones from patients, but not from controls, reactive specifically to the insulin secretory enriched fraction (ISG) of a rat insulinoma RIN cell line. This finding is suggestive of an in vivo priming by the antigen(s). To examine the relevance of these T cell clones in the pathogenesis of IDDM, we studied their cytokine profile. T cell clones from the newly onset patients had a Th1 cytokine profile, while those from the prediabetic patient were of the Th2 subtype. This segregation suggests that RIN-ISG contains antigen(s) involved in the pathogenesis of this disease, since IDDM is considered a cell-mediated or Th1 disease. Since two of these clones also responded to a hamster insulinoma cell line HIT, at least two antigens in RIN-ISG could be defined by this panel of T cell clones. Examination of CDR3 sequences confirmed the clonality of the dual-reactive T cell clones. The finding of HIT-reactive cells in IDDM patients may be useful in efforts to identify prediabetic patients for immune intervention. Dual reactivity may provide a better prognosis than single reactivity. In contrast to T cell clones reactive to insulinomas, T cell clones reactive to normal human ISG were not found after over 200 clones were screened. In addition, RIN-ISG specific clones did not respond to either normal human or rat ISG, suggesting that IDDM antigens are below detectable levels in normal beta cells.
authors.affiliation: Immune Response Corporation, Carlsbad, CA 92008, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Chang
authors.forename: L G
authors.initials: LG
authors.lastname: Linarelli
authors.forename: J A
authors.initials: JA
authors.lastname: Laxer
authors.forename: K J
authors.initials: KJ
authors.lastname: Froning
authors.forename: L L
authors.initials: LL
authors.lastname: Caralli
authors.forename: S W
authors.initials: SW
authors.lastname: Brostoff
authors.forename: D J
authors.initials: DJ
authors.lastname: Carlo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002999:Clone Cells / Q000276:immunology; D006224:Cricetinae; D003594:Cytoplasmic Granules / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D007340:Insulinoma / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000378:metabolism; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000473:pathology; D011236:Prediabetic State / Q000276:immunology / Q000473:pathology; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D008222:Lymphokines