Priming of immature thymocytes to CD3-mediated apoptosis by infection with murine cytomegalovirus.
Cytomegalovirus (CMV) causes severe clinical manifestations in immunocompromised hosts; however, it remains unclear whether the virus itself is a cause of immunosuppression or whether it is involved as an opportunistic bystander pathogen. This study was performed to elucidate the effect of CMV infection on the host's immune system. The double-positive thymocytes of BALB/c mice inoculated with a sublethal dose of murine CMV (MCMV) were extensively depleted by a 10-micrograms amount of anti-CD3 monoclonal antibody, while such an amount was unable to induce any apparent elimination of thymocytes in noninfected mice. In immature thymocytes of infected hosts, a markedly high level of susceptibility to apoptosis induction was found on treatment with anti-CD3 monoclonal antibody. Analysis of the signal transduction pathway of such double-positive thymocytes demonstrated a profound elevation of the intracellular Ca2+ level after anti-CD3 stimulation, implying that this aberrant mobilization of Ca2+ plays a crucial role in the signaling pathway leading these cells to an extensive apoptosis. Examination of the thymus by PCR was able to detect a low copy number of MCMV DNAs in thymic stromal cells but none at all in thymocytes. Therefore, it is suggested that a mechanism which is not associated with virus replication within the cells exerts a critical effect on rendering the thymocytes highly apoptosis sensitive in hosts infected with MCMV.
Koga
Y
Y
Department of Infectious Disease, School of Medicine, Tohkai University, Kanagawa, Japan.
Tanaka
K
K
Lu
Y Y
YY
Oh-Tsu
M
M
Sasaki
M
M
Kimura
G
G
Nomoto
K
K
D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis; D001483:Base Sequence; D017252:CD3 Complex / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D003587:Cytomegalovirus / Q000302:isolation & purification / Q000502:physiology*; D017931:DNA Primers; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D015398:Signal Transduction; D013950:Thymus Gland / Q000166:cytology* / Q000382:microbiology / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D017931:DNA Primers; D002118:Calcium