EVIDENCE FOR A NONCLASSICAL PATHWAY OF GRAFT-REJECTION INVOLVING INTERLEUKIN-5 AND EOSINOPHILS

The role of IL-5 and eosinophils in allograft rejection was studied in human liver allograft recipients. Liver allograft biopsies were analy zed for intragraft IL-5 gene expression, and the percentages of eosino phils and plasma cells within the portal infiltrate as well as periphe ral eosinophil levels were determined. The majority of allografts with evidence of rejection had concomitant IL-5 mRNA and eosinophilia, whi le no resolving or nonrejecting allografts had simultaneous IL-5 mRNA and eosinophilia. In fact, rejecting liver allografts that contain IL- 5 mRNA and eosinophils also contain infiltrating cells that produce th e cytotoxic mediator major basic protein. In contrast, intragraft plas ma cell and peripheral eosinophil levels did not correlate with the hi stopathologic status of the allograft. Cyclosporine and FK506 had simi lar effects on the frequency of IL-5 gene expression in rejecting and nonrejecting allografts. However, OKT3 appeared to profoundly modulate IL-5 gene expression, since 0 of 11 biopsies obtained during OKT3 tre atment for rejection contained IL-5 transcripts. These observations ra ise the possibility of a cellular pathway of liver allograft rejection mediated by IL-5-activated eosinophils.