PRIMING OF IMMATURE THYMOCYTES TO CD3-MEDIATED APOPTOSIS BY INFECTIONWITH MURINE CYTOMEGALOVIRUS

Cytomegalovirus (CMV) causes severe clinical manifestations in immunoc ompromised hosts; however, it remains unclear whether the virus itself is a cause of immunosuppression or whether it is involved as an oppor tunistic bystander pathogen. This study was performed to elucidate the effect of CMV infection on the host's immune system. The double-posit ive thymocytes of BALB/c mice inoculated with a sublethal dose of muri ne CMV (MCMV) were extensively depleted by a 10-mu g amount of anti-CD 3 monoclonal antibody, while such an amount was unable to induce any a pparent elimination of thymocytes in noninfected mice. In immature thy mocytes of infected hosts, a markedly high level of susceptibility to apoptosis induction was found on treatment with anti-CD3 monoclonal an tibody. Analysis of the signal transduction pathway of such double-pos itive thymocytes demonstrated a profound elevation of the intracellula r Ca2+ level after anti-CD3 stimulation, implying that this aberrant m obilization of Ca2+ plays a crucial role in the signaling pathway lead ing these cells to an extensive apoptosis. Examination of the thymus b y PCR was able to detect a low copy number of MCMV DNAs in thymic stro mal cells but none at all in thymocytes. Therefore, it is suggested th at a mechanism which is not associated with virus replication within t he cells exerts a critical effect on rendering the thymocytes highly a poptosis sensitive in hosts infected with MCMV.