Murine model of interstitial cytomegalovirus pneumonia in syngeneic bone marrow transplantation: Persistence of protective pulmonary CD8-T-cell infiltrates after clearance of acute infection

Interstitial pneumonia (IP) is a severe organ manifestation of cytomegalovi rus (CMV) disease in the immunocompromised host, in particular in recipient s of bone marrow transplantation (BMT). Diagnostic criteria for the definit ion of CMV-IP include clinical evidence of pneumonia together with CMV dete cted in bronchoalveolar lavage or lung biopsy. We have used the model of sy ngeneic BMT and simultaneous infection of BALB/c mice with murine CMV for s tudying the pathogenesis of CMV-TP by controlled longitudinal analysis. A d isseminated cytopathic infection of the lungs with fatal outcome was observ ed only when reconstituting CD8 T cells were depleted. Neither CD8 nor CD4 T cells mediated an immunopathogenesis of acute CMV-IP, By contrast, after efficient hematolymphopoietic reconstitution, viral replication in the lung s was moderate and focal. The histopathological picture was dominated by pr eferential infiltration of CD8 T cells confining viral replication to infla mmatory foci. Notably, after clearance of acute infection, CD62L(lo) and CD 62L(hi) subsets of CD44(+) memory CDS T cells were found to persist in lung tissue. One can thus operationally distinguish an early CMV-positive IP (p hase 1) and a late CMV-negative IP (phase 2), According to the definition, phase 2 histopathology would not be diagnosed as a CMV-IP and could instead be misinterpreted as a CMV-induced immunopathology. We document here that phase 1 as well as phase 2 pulmonary CD8 T cells are capable of exerting ef fector functions and are effectual in protecting against productive infecti on. We propose that antiviral "stand-by" memory-effector T cells persist in the lungs to prevent virus recurrence from latency.