Site-restricted Persistent Cytomegalovirus Infection after Selective Long-term Depletion of Cd4` T Lymphocytes by Stipan Jonjic,'

Cytomegalovirus (CMV)infections are controlled by the immune system and lead to viral latency (1) in the immunocompetent host . Only in the immunocompromised host do primary as well as recurrent infections cause fatal disease. Congenital infection is responsible for severe fetal malformation (2, 3), and interstitial CMV pneumonia is considered the main reason for mortality in leukemia patients irradiated for bone marrow transplantation (4). Manifestations of CMV disease have been reported as episymptoms of AIDS, frequently representing the immediate cause of death after immunosuppression by HIV (5). We have previously described an animal model for the study ofCMV disease in the whole-body -y-irradiated host, the infection of mice with murine CMV (MCMV)' . By adoptive cell transfer, protection against acute MCMV disease proved a function of specifically sensitized effector T lymphocytes of the CD8 subset, whereas T lymphocytes of the CD4 subset were dispensable for short-term immunocytotherapy (6-9) . The CD8+ effector cells prevented the lethal bone marrow aplasia caused by a virus-induced failure in hemopoietic stem cell generation (10), and also prevented tissue lesions by controlling the spread of virus (8). The immunodominant antigen recognized by protective, antiviral CD8+ T lymphocytes could be identified as a family of peptides derived from pp89, the major immediate-early phase protein encoded by MCMV (11-17) . Theconditions for superimposed CMV disease during HIV infection differ from those in bone marrow transplant recipients in that the immunosuppression selectively affects the CD4+ T lymphocytes, while sparing the CD8+ T lymphocytes (18) . It was therefore of interest to explore to what extent the residual CD8 subset can control CMV infection on its own. Recent reports have given examples for an autonomy in vivo of the CD8 subset in viral infection models involving a depletion of the CD4 subset (19-22), which implies that cooperation of CD4+ helper T lymphocytes is not essential for initiating a CD8 subset-mediated immune response . Whether such a response can last long enough to also maintain a long-term control