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Initial characterization of humoral IL-2 response inhibition following donor-specific transfusions under azathioprine
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.
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.