Individual differences in the in vitro response to cyclosporin A (CsA): possible heterogeneity in the involvement of the CD28-B7/BB1 pathway.
Differences in the response of graft recipients to the immunosuppressive effect of cyclosporin A (CsA) represent a major factor of allograft acceptance. Response to CsA was investigated in vitro in 59 healthy subjects by measuring the inhibition of lymphocyte proliferation and interleukin-2 (IL-2) production. Marked differences were found comparing individuals: 61% of the subjects responded with half inhibitory doses ID50 < 200 ng/ml (responder group), 20% with ID50 within 200-400 ng/ml (intermediate responder) and 19% were non responder with ID50 > 400 ng/ml and sometimes over 1,000 ng/ml. To explain these differences, the CD28-B7, co-stimulatory pathway for T-cell activation was explored since it is the only CsA-resistant pathway known so far. Both responder and non responder individuals showed increased proliferative response and IL-2 secretion by co-stimulation with CD3 and CD28, resulting in increased ID50 by a similar factor. The percentage of CD28+ cells within T-lymphocytes varied markedly among subjects (48.5 +/- 28.9% of the CD8+ cells). However we could not correlate the inter-individual variation of sensitivity to CsA to the size of the CD8+CD28+ T cell subset nor to divergent response to CD3 and CD28 co-stimulation.
Masy
E
E
Service d'Immunologie, Centre hospitalier régional et universitaire de Lille, France.
Labalette-Houache
M
M
Dessaint
J P
JP
D000328:Adult; D018106:CD28 Antigens / Q000032:analysis / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000737:chemistry; D013601:T-Lymphocytes / Q000166:cytology*
D018106:CD28 Antigens; D016572:Cyclosporine