HUMAN CYTOMEGALOVIRUS EARLY INFECTION, ACUTE REJECTION, AND MAJOR HISTOCOMPATIBILITY CLASS-II EXPRESSION IN TRANSPLANTED LUNG - MOLECULAR, IMMUNOCYTOCHEMICAL, AND HISTOPATHOLOGIC INVESTIGATIONS

The present study aimed to investigate the relationship between acute rejection and human cytomegalovirus (HCMV) infection, as well as the c oexpression of HLA-DR and immediate-early (IE) viral antigens, in 143 transbronchial biopsies and broachoalveolar lavage fluids of 32 lung t ransplant recipients, We investigated the occurrence of morphologicall y overt viral infection with conventional histopathology, the expressi on of IE antigens with single labeling immunohistochemistry, the coexp ression of IE antigens and HLA-DR molecules with double labeling techn iques, and the presence of viral IE genes with polymerase chain reacti on (PCR). Histopathologic study showed overt viral infections (12.6%) in 18 of the 143 biopsies; 8 were in a context of pneumonia and 10 wer e localizations without surrounding inflammatory cells; immunohistoche mistry showed IE viral antigen expression in 31 (21.67%); PCR detected viral IE genes in 73/143 lavage fluids and biopsies (51%), The double labeling immunohistochemical technique showed that most IE antigen-ex pressing, noncytopathic cells were either HLA-DR negative in areas wit hout infiltrates, or HLA-DR positive in those areas where inflammatory infiltrates were consistent, in the absence of viral cytopathy, with acute rejection. The results indicate that, in transplanted lung, the frequency of morphologically occult HCMV infection (as detected by imm unohistochemistry and/or PCR) is much higher than that of morphologica lly overt viral infection. The occurrence of inflammatory infiltrates (consistent with acute rejection) around morphologically occult infect ed cells and the possible lack of inflammation around both early- and late-infected cells suggest that in biopsies with occult infection the infiltrates should be attributed to allograft reaction. This conclusi on would be in keeping with the coexpression of HLA-DR and HCMV IE in infiltrate-rich biopsies that are consistent with acute rejection, as well as with the absence of HLA-DR expression in IE antigen-positive c ells in infiltrate-free areas.