Islet T Cells Secreting IFN-γ in NOD Mouse Diabetes: Arrest by p277 Peptide Treatment (original) (raw)

1998, Journal of Autoimmunity

Non-obese diabetic (NOD) mice spontaneously develop insulin-dependent (type 1) diabetes mellitus (IDDM) caused by T cells which destroy the insulin-producing islet -cells. Since cytokines are involved in this autoimmune -cell damage, we used an ELISPOT assay to enumerate the isletassociated T cells that secreted interferon-gamma (IFN-), tumor necrosis factor-alpha (TNF-) or interleukin-4 (IL-4). We used mitogenic anti-CD3 antibody to activate all the T cells capable of responding, irrespective of their antigen specificity. We found that NOD females, more susceptible than males to IDDM, accumulated islet IFN-producers more rapidly with age than did the males. Acceleration of male IDDM by cyclophosphamide led to a marked increase in IFN-secreting islet T cells. In contrast, a decrease in IFN-producing islet T cells was associated with arrest of IDDM by administration of peptide p277 of the 60 kDa heat-shock protein (hsp60) to 12-week-old female NOD mice. The p277-treated mice later manifested a greater number of islets and fewer leukocytes per islet than did the mice treated with a bacterial hsp60 peptide. Thus, the development of diabetes could be correlated with the accumulation in the islets of T cells producing IFN-, and destructive insulitis could be downregulated by the administration of a single peptide.

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