The effects of 3‐hydroxybutyrate and glucose on human T cell responses to Candida albicans

Diabetic patients are particularly susceptible to mucocutaneous candidosis. T lymphocytes are central to the induction of antigen‐specific immune 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 concentrations of glucose and 3‐hydroxybutyrate (3‐HB) in cultures of human T cells stimulated with Candida albicans antigen. Proliferation of T cells from six type 1 diabetic and six non‐diabetic control subjects was significantly inhibited (both P <0.05) in glucose‐free medium, and at a glucose concentration of 80 mmol 1 −1 as compared with cultures containing glucose at physiological concentration (5 mmol 1 −1 ). 16 and 32 mmol 1 −1 3‐HB also inhibited T cell proliferation in the presence of 5 mmol 1 −1 glucose ( P <0.05). The effect of glucose and 3‐HB were not additive and the inhibition was not due to cell death. 32 mmol 1 −1 3‐HB had less effect when present solely during antigen pulsing than during subsequent lymphocyte stimulation, and was effective even when added after 72 h of a six day culture. This suggests that ketosis affects T cell proliferation more than antigen processing and presentation. We conclude that human antigen‐specific T cell proliferation 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 cell function under such extreme conditions could be implicated in the close association of diabetic ketoacidosis with deep fungal infections, particularly invasive mucormycosis.