Effect of insulin and transferrin in the maintenance of the activated state of the T-lymphocyte induced by allo-antigen.

Insulin is an immuno-modulating molecule enhancing cytotoxic T-cell function and supporting intermediary metabolism in activated lymphocytes. Insulin also maintains the activated state of mitogen-stimulated lymphocytes. Because of the importance of allo-antigen response of diabetic patients for infections and transplant immunity, we explored the role of insulin in the allo-activated state of lymphocytes. Allo-stimulation was provided in one-way mixed lymphocyte reactions, with Balb/C mouse lymph node cells responding to irradiated spleen cells of C57BL/6 mice, in culture under conditions which permitted evaluation of hormonal modulation. Mixed lymphocyte reactions established in fetal calf serum, insulin-depleted by passage over antibody affinity columns, were of equal magnitude to those in insulin-replete serum. A weak but positive mixed lymphocyte reaction can be effected with an artificial serum substitute containing no additional hormone. Provision of insulin (10 nmol/l) restored a full mixed lymphocyte reaction response which was mimicked by addition of transferrin. The insulin-transferrin combination was not additive. In conclusion, insulin and transferrin maintain the allo-activated state of the mouse lymphocyte, transferrin alone being sufficient when full antigenic stimulation is provided. If the same applies to human lymphocytes, insulin-deficient diabetic patients will respond to full allo-antigen challenge, and so should be fully capable of mounting a transplant immune response.