Document 0913
 DOCN  M95A0913
 TI    Insulin-secretory-granule specific T cell clones in human IDDM.
 DT    9510
 AU    Chang JC; Linarelli LG; Laxer JA; Froning KJ; Caralli LL; Brostoff SW;
       Carlo DJ; Immune Response Corporation, Carlsbad, CA 92008, USA.
 SO    J Autoimmun. 1995 Apr;8(2):221-34. Unique Identifier : AIDSLINE
       MED/95336597
 AB    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.
 DE    Amino Acid Sequence  Animal  Base Sequence  Clone Cells/IMMUNOLOGY
       Cytoplasmic Granules/*IMMUNOLOGY  Diabetes Mellitus,
       Insulin-Dependent/*IMMUNOLOGY/PATHOLOGY  Gene Rearrangement, beta-Chain
       T-Cell Antigen Receptor  Hamsters  Human
       Insulinoma/IMMUNOLOGY/PATHOLOGY  Lymphocyte Transformation
       Lymphokines/SECRETION  Molecular Sequence Data  Neoplasms,
       Experimental/IMMUNOLOGY/PATHOLOGY  Pancreatic
       Neoplasms/IMMUNOLOGY/PATHOLOGY  Prediabetic State/IMMUNOLOGY/PATHOLOGY
       Rats  T-Lymphocyte Subsets/*IMMUNOLOGY  Th1
       Cells/IMMUNOLOGY/PATHOLOGY/SECRETION  Th2
       Cells/IMMUNOLOGY/PATHOLOGY/SECRETION  Tumor Cells, Cultured  JOURNAL
       ARTICLE

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