Cytokine secretion patterns in twins discordant for Type I diabetes

Aims/hypothesis. The search for T-cell reactions that are associated with d isease in Type I (insulin-dependent) diabetes mellitus is severely hampered because control groups cannot be matched for relevant immune response gene s. We therefore compared T-cell responses between identical twins discordan t for Type I diabetes. Methods. Pairs of monozygotic twins (n = 17) discordant for Type I diabetes were studied. Cultures were set up from whole blood immediately after samp ling and cells were challenged with human recombinant hsp60. with the mitog en phytohaemagglutinin or with the staphylococcal superantigen. Supernatant s were removed after 48 or 96 h and analysed for T-helper1 type cytokines i nterferon-gamma, TNF alpha. and T-helper2 type cytokines IL-4, IL-10 by san dwich-ELISA. Results. The height of the T-helper1 type cytokine response to hsp60, phyto haemagglutinin or staphylococcal enterotoxin B did not show disease associa tion, i.e. it was similar between discordant twins. In contrast, the produc tion of T-helper2 type cytokines differed between discordant twins. The IL- 10 response to hsp60 was higher in twins at low disease risk (islet cell an tibody-negative) than in their diabetic cotwins (p < 0.01), as was the IL-4 response to phytohaemagglutinin (p < 0.05). No difference was seen in the cytokine response between islet cell antibody-positive twins and their diab etic cotwins. Conclusions/interpretation. The data indicate an association between T-help er2 type cytokine secretion patterns and disease or disease risk.