INDUCTION OF APOPTOSIS OF T-CELLS BY INFECTING MICE WITH MURINE CYTOMEGALOVIRUS

Cytomegalovirus (CMV) is associated with several lymphocyte dysfunctio ns, but the precise mechanisms of the dysfunctions are still unclear, To elucidate the mechanisms, a cell cycle-DNA content analysis was per for med 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 high er percentage of hypodiploid nuclei after 12 or 24 h of culture than t hose from naive mice, T cells from infected mice also contained a larg er amount of fragmented DNA, Taken together, these results suggested t hat infection with MCMV induced the apoptotic cell death of T cells, T his induction of apoptosis accounted for the dysfunction of lymphocyte s, 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 m ight be the cause of the apoptosis of cells, T cells from MCMV-infecte d C57BL/6-lpr/lpr mice with mutations at the lpr/fas locus, however, a lso showed a substantial level of apoptosisl which was reproducibly lo wer than that seen in C57BL/6 mice, Therefore, it was suggested that t he Fas-mediated pathway contributed to but was not sufficient for the induction of apoptosis and that mechanisms other than the Fas-associat ed pathway were also involved in the induction of apoptosis.