Initial characterization of humoral IL-2 response inhibition following donor-specific transfusions under azathioprine immunosuppression.
A previous study indicated that noncompetitive humoral inhibition of IL-2-induced proliferation was a frequent consequence of donor-specific transfusions under azathioprine immunosuppression. In this report, we present our initial characterization of the mode of action and nature of this humoral activity. A direct role for azathioprine seems unlikely since its removal from post-DST+A sera did not eliminate inhibition, nor did addition of azathioprine to normal sera mimic the inhibition by post-DST+A sera. Inhibition of the proliferative response to IL-2 was observed on an individual cell basis after IL-2 stimulation that did not involve a direct effect on DNA synthesis. Inhibition appeared to require optimal IL-2 receptor expression as well as optimal doses of IL-2, suggesting that inhibition is manifested at the postreceptor level. Inhibition could not be removed by reconstitution with normal sera, indicating that post-DST+A sera were not deficient in a nominal serum component, which is necessary for optimal proliferation. The inhibitory activity in post-DST+A sera was sensitive to chemical reduction and heat. Inhibition of the response to IL-2 was readily demonstrated using IL-2 responsive human or murine T lymphocytes. However, post-DST+A serum also inhibited proliferation of one of two IL-2 independent cell lines. These results suggest that the inhibitory activity in post-DST+A plasma/serum may be due to the induction of an inhibitor of cell proliferation that is either lacking or "deficient" in normal serum.
D000917:Antibody Formation / Q000187:drug effects*; D001379:Azathioprine / Q000627:therapeutic use*; D001804:Blood Transfusion, Autologous; D003956:Dialysis; D004305:Dose-Response Relationship, Drug; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000494:pharmacology*; D008623:Mercaptoethanol / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism
D007376:Interleukin-2; D008623:Mercaptoethanol; D001379:Azathioprine; D013936:Thymidine