THE EOSINOPHIL AS AN EFFECTOR CELL OF THE IMMUNE-RESPONSE DURING HEPATIC ALLOGRAFT-REJECTION

Objective: To evaluate the role of the eosinophil granulocyte during h epatic allograft rejection. Design: (a) A retrospective case-control s tudy and (b) a prospective study of consecutive liver transplant recip ients. Patients: In the retrospective study, eight patients with sever e rejection in the first month after liver transplantation were compar ed with six patients without rejection. In the prospective study, 20 c onsecutive patients were studied for the presence of liver allograft r ejection between March 1989 and October 1989. Measurements: Absolute e osinophil counts were determined whenever blood was drawn. Serum was a nalyzed for the presence of two eosinophil granule proteins, major bas ic protein and eosinophil-derived neurotoxin, on days 7, 14 and 21 aft er transplantation. Liver biopsy specimens were stained for the presen ce of major basic protein by means of immunofluorescence using a doubl e-antibody staining technique. The degree of eosinophil infiltration a nd degranulation was graded using a panel of representative slides. Re sults: Blood eosinophilia was increased in patients with hepatic allog raft rejection (p < 0.05). Serum major basic protein and eosinophil-de rived neurotoxin concentrations were similar in patients with and with out rejection. Many portal tracts of patients with rejection contained an abundance of eosinophils, and staining for major basic protein rev ealed the presence of intact eosinophils. In addition, extracellular m ajor basic protein was seen, sometimes in the absence of intact eosino phils or an extensive infiltrate. In patients with severe allograft re jection, major basic protein staining was present in littoral cells li ning the sinusoids. Conclusions: Patients with severe rejection in the first month after liver transplantation often have blood eosinophilia and marked infiltration of portal tracts with eosinophils or evidence of eosinophil degranulation. The presence of major basic protein like ly is direct evidence of tissue destruction and may indicate active re jection (major basic protein in eosinophils and extracellular major ba sic protein, presence of portal infiltrate) or the immediate postinfla mmatory rejection state (extracellular major basic protein and major b asic protein inside littoral cells, absence of portal infiltrate and e osinophils, bile ducts damaged or vanished). These findings underline the importance of the eosinophil as an integral part of the rejection process. We conclude that the presence of eosinophils or their secreti on products in the first month after liver transplantation is an indic ator of ongoing or recent allograft rejection.