Induction of apoptosis of T cells by infecting mice with murine cytomegalovirus.
Cytomegalovirus (CMV) is associated with several lymphocyte dysfunctions, but the precise mechanisms of the dysfunctions are still unclear. To elucidate the mechanisms, a cell cycle-DNA content analysis was performed on splenic T cells of murine CMV (MCMV)-infected BALB/c mice. T cells from mice infected with 3 x 10(3) PFU of MCMV contained a higher percentage of hypodiploid nuclei after 12 or 24 h of culture than those from naive mice. T cells from infected mice also contained a larger amount of fragmented DNA. Taken together, these results suggested that infection with MCMV induced the apoptotic cell death of T cells. This induction of apoptosis accounted for the dysfunction of lymphocytes, at least partially. Flow cytometric analysis showed that T cells as well as B cells from MCMV-infected mice expressed an augmented level of Fas antigen, an apoptosis-associated cell surface molecule, which might be the cause of the apoptosis of cells. T cells from MCMV-infected C57BL/6-lpr/lpr mice with mutations at the lpr/fas locus, however, also showed a substantial level of apoptosis, which was reproducibly lower than that seen in C57BL/6 mice. Therefore, it was suggested that the Fas-mediated pathway contributed to but was not sufficient for the induction of apoptosis and that mechanisms other than the Fas-associated pathway were also involved in the induction of apoptosis.
Yoshida
H
H
Department of Immunology, Kyushu University, Fukuoka, Japan.
Sumichika
H
H
Hamano
S
S
He
X
X
Minamishima
Y
Y
Kimura
G
G
Nomoto
K
K
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001483:Base Sequence; D005260:Female; D005814:Genes, Viral; D006566:Herpesviridae Infections / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018146:Muromegalovirus / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology*