IL-2 AND IL-5 GENE-EXPRESSION IN RESPONSE TO ALLOANTIGEN IN LIVER ALLOGRAFT RECIPIENTS AND INVITRO

IL-2 and IL-5 gene expression in response to alloantigen was studied i n liver allograft recipients and in an in vitro system. Seventy-seven sequential liver allograft biopsies from 22 patients were analyzed for IL-2 and IL-5 mRNA by polymerase chain reaction and Southern blot hyb ridization. Message for IL-5 was present in 74% of allografts with rej ection, 46% of allografts with resolving rejection, and 33% of allogra fts with no evidence of rejection. The frequency of IL-5 transcripts i n rejecting allografts was significantly different than the frequency of IL-5 transcripts in grafts without evidence of rejection (P = 0.003 ). Message for IL-2 was detected in 29% of rejecting allografts, 18% o f allografts without evidence of rejection, and 43% of allografts with resolving rejection. There was no significant association between IL- 2 gene expression and the histopathological status of the allograft. I nterestingly, 9 of 15 biopsies that contained IL-2 message in the no r ejection and resolving rejection categories went on to display rejecti on shortly thereafter. IL-2 and IL-5 gene expression rarely occurred s imultaneously within allografts. An in vitro system consisting of irra diated, allogeneic stimulator cells and normal peripheral blood mononu clear cells as responders was established to further investigate alloa ntigen-driven IL-2 and IL-5 production. Both IL-2 and IL-5 were produc ed in response to alloantigen as determined by specific bioassays. Max imal levels of IL-5 activity in culture supernatants generally followe d maximal IL-2 levels by 24 hr, but both IL-2 and IL-5 production were dramatically inhibited by CsA. Analysis of cytokine gene expression r evealed that IL-2 transcription peaked within the initial 24 hr of cul ture, whereas IL-5 transcription was maximal at 120 hr of culture. The expression of a CTL-specific serine esterase gene was similar to IL-5 in that it was maximal during the latter phases of the culture period . Thus, both human IL-2 and IL-5 are produced in response to alloantig en and are inhibitable by CsA. These data suggest that IL-2 and IL-5 m ay participate in cellular pathways of tissue damage within the reject ing allograft.