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.
Gregory
R
R
Department of Diabetes, University Hospital, Queen's Medical Centre, Nottingham, UK.
McElveen
J
J
Tattersall
R B
RB
Todd
I
I
D020155:3-Hydroxybutyric Acid; D000328:Adult; D000938:Antigen-Presenting Cells / Q000187:drug effects; D002176:Candida albicans / Q000276:immunology*; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D006885:Hydroxybutyrates / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D006885:Hydroxybutyrates; D005947:Glucose; D020155:3-Hydroxybutyric Acid