Modulation of the response to interleukin 2 in recipients of donor-specific transfusions under azathioprine immunosuppression.
The effect of plasma from recipients of donor-specific transfusions given under azathioprine immunosuppression (DST+A) on the response to IL-2 was examined. Pre-DST+A plasma markedly enhanced the proliferative response to suboptimal doses of IL-2 by IL-2-dependent T cells, such that maximal responsiveness was achieved at lower IL-2 doses, as compared with normal plasma. Post-DST+A plasma also enhanced the response to suboptimal IL-2 doses. However at saturating IL-2 doses, the maximum response was markedly inhibited by post-DST+A plasma as compared with normal or pre-DST+A plasma. Neither toxicity nor inhibition of the IL-2 response was observed when the IL-2-dependent indicator cells were preincubated in post-DST+A plasma prior to an IL-2 dose-response assay. Of the recipients whose plasma was examined, nearly all exhibited some degree of inhibition (range: 8-50% inhibition) of the response to saturating levels of IL-2. Only one renal allograft has been lost in these recipients due to rejection, and this was an accelerated acute rejection in a recipient who had rejected 2 previous allografts and who developed a "transient" positive crossmatch to his donor during DST+A. The results suggest that inhibition of IL-2 responsiveness may be a frequent consequence of DST+A, and that the inhibition is dependent on an IL-2-mediated effect distinct from proliferation. Thus, such inhibition may contribute to the salutary effect of DST+A on renal transplantation.
D001379:Azathioprine / Q000494:pharmacology*; D001803:Blood Transfusion; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007165:Immunosuppression Therapy; D007376:Interleukin-2; D016030:Kidney Transplantation; D007959:Lymphocyte Culture Test, Mixed
D007376:Interleukin-2; D001379:Azathioprine