
MODULATION OF THE RESPONSE TO INTERLEUKIN 2 IN RECIPIENTS OF DONOR-SPECIFIC TRNSFUSIONS UNDER AZATHIOPRINE IMMUNOSUPPRESSION
Author(s) -
John D. Tyler,
Charles B. Anderson,
Gregorio A. Sicard
Publication year - 1986
Publication title -
transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.45
H-Index - 204
eISSN - 1534-6080
pISSN - 0041-1337
DOI - 10.1097/00007890-198611000-00012
Subject(s) - immunosuppression , azathioprine , endocrinology , medicine , chemistry , immunology , disease
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.