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 l-1 as compared with cultures containing glucose at physiological concentration (5 mmol l-1). 16 and 32 mmol l-1 3-HB also inhibited T cell proliferation in the presence of 5 mmol l-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 l-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.