THE EFFECTS OF 3-HYDROXYBUTYRATE AND GLUCOSE ON HUMAN T-CELL RESPONSES TO CANDIDA-ALBICANS

Diabetic patients are particularly susceptible to mucocutaneous candid osis. T lymphocytes are central to the induction of antigen-specific i mmune responses and may be sensitive to the biochemical abnormalities associated with poorly controlled diabetes; namely, hyperglycaemia and /or ketonemia. To examine this we have studied the effect of varying c oncentrations of glucose and 3-hydroxybutyrate (3-HB) in cultures of h uman T cells stimulated with Candida albicans antigen. Proliferation o f T cells from six type 1 diabetic and six non-diabetic control subjec ts was significantly inhibited (both P<0.05) in glucose-free medium, a nd at a glucose concentration of 80 mmol l(-1) as compared with cultur es containing glucose at physiological concentration (5 mmol l(-1)). 1 6 and 32 mmol l(-1) 3-HB also inhibited T cell proliferation in the pr esence of 5 mmol l(-1) glucose (P<0.05). The effect of glucose and 3-H B were not additive and the inhibition was not due to cell death. 32 m mol l(-1) 3-HB had less effect when present solely during antigen puls ing than during subsequent lymphocyte stimulation, and was effective e ven when added after 72 h of a six day culture. This suggests that ket osis affects T cell proliferation more than antigen processing and pre sentation. We conclude that human antigen-specific T cell proliferatio n is inhibited in vitro only by concentrations of 3-HB encountered in moderately severe diabetic ketoacidosis, and by glucose concentrations found in severe hyperosmolar non-ketotic coma. The impairment of T ce ll function under such extreme conditions could be implicated in the c lose association of diabetic ketoacidosis with deep fungal infections, particularly invasive mucormycosis.