In Vitro Secretion of Interleukin 2 and Expression of IL-2 Receptor in Peripheral Blood Lymphocytes in High Risk of Insulin-Dependent Diabetes Mellitus Subjects

Interleukin 2 (IL-2) – a Th1 lymphocyte-derived cytokine is at present considered to play an important r ole in the etiopathogenesis of insulin-dependent diabetes mellitus. In the previous studies increased, decreased a nd unchanged IL-2 levels in patients with recent onset of insulin-dependent diabetes mellitu s (IDDM) were found. These differences could be a result of different metabolic status or/and a different stage of the autoimmune p rocess. The aim of our study was to estimate in vitro secretion of IL-2 and CD25 antigen expression by the p eripheral blood T lymphocytes in subjects at the preclinical stage of IDDM (prediabetes), b ut still without metabolic disturbances. In 27 first degree relatives of IDDM patients with antibodies against different pancreatic i slet cell antigens (ICA, GADA, IAA, IA-2) CD25 antigen expression on peripheral blood lymphoc ytes T was measured by flow cytometry and IL-2 concentration in supernatants of 48 and 72 h cultures of peripheral whole b lood with 10 μg /ml PHA was estimated by ELISA. The control group was comprised of 34 age and sex-matched healthy volunteers. In the studied high risk IDDM subjects the decreased CD25 expression in pe ripheral CD4 l ymphocytes T and a negative correlation between the percentage of CD25 cells and islet cell antibodies (ICA) t itres was observed. No differences in IL-2 levels in supernatants of 48 h and 72 h blood cult ures was found in subjects with single antibody (ICA) in comparison to healthy controls. A significant increase of IL-2 secretion a t 72 h of PHA stimulation was shown in first degree relatives of IDDM patients with a combina tion of 3 or more antipancreatic-B cell antibodies. There were also a significant negative correlation between glutamic acid d ecarboxylase antibodies (GADA) titres and IL-2 levels in 72 h of culture. The present study suggests the i nvolvement of IL-2 in the pathogenesis of IDDM. The estimation of CD25 antigen expression in the peripheral b lood lymphocytes could be an additional immunological marker of identification of subje cts in prediabetes.

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