Increased cyclosporine sensitivity of T cells from cord blood compared with those from the adult.
Despite the increasing numbers of paediatric transplants performed, little is known about the immune responses of T lymphocytes in human neonates. Here we have compared the effects of cyclosporine on the phytohaemagglutinin (PHA) response of immature (cord) and mature (adult) lymphocytes using the following parameters of activation: (i) proliferation, measured by 3H-thymidine uptake; (ii) expression of cell surface IL-2 receptor; (iii) release of IL-2 into the supernatant. Cyclosporine was added to cultures of PHA-stimulated lymphocytes at doses ranging from 5 to 5000 ng/ml. The proliferative response of cord lymphocytes was considerably more sensitive to cyclosporine at each dose, so that 50% inhibition was achieved by 6 ng/ml and 21.5 ng/ml doses of cyclosporine on cord and adult lymphocytes, respectively. Expression of the IL-2 receptor by PHA-activated T cells and their subsets was assessed by flow cytometry. Cyclosporine inhibited IL-2 receptor expression to a significantly greater degree in cord CD4 and CD8 cells (49.7% and 70.1%) than in adults (17.9% and 30.0%). Biologically active IL-2 release was measured using the IL-2-dependent cell line CTLL-2. Cyclosporine at doses 50-5000 ng/ml produced 80-99% inhibition of both cord and adult responses. However, at very low doses (5 ng/ml) cyclosporine produced 69.3% inhibition of cord lymphocytes, compared with 42.0% of adult lymphocytes. These results suggest that the T cells of neonates are considerably more sensitive to cyclosporine than are adult T cells.
McDouall
R M
RM
Heart Science Centre, Harefield Hospital, UK.
Suitters
A J
AJ
Smith
H
H
Yacoub
M H
MH
Rose
M L
ML
D000328:Adult; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D007231:Infant, Newborn; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D010835:Phytohemagglutinins / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects*
D007376:Interleukin-2; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D016572:Cyclosporine