Objective. To analyze Fas and tumor necrosis factor receptor I (TNFRI) apop
tosis pathways in salivary gland inflammatory disease induced by murine cyt
omegalovirus (MCMV) infection.
Methods. Four different strains of mice (C57Bl/6 [B6]-+/+, Fas-deficient B6
-lpr/lpr, TNFRI-deficient B6-tnfr1(0/0), and B6-tnfr1(0/0)-lpr/lpr mice) we
re infected intraperitoneally with the Smith strain of MCMV (1 x 10(5) plaq
ue-forming units). Viral load was determined by a plaque assay, inflammatio
n and apoptosis by immunohistochemistry and staining with terminal dUTP nic
k-end labeling, and autoantibodies by enzyme-linked immunosorbent assay.
Results. Infectious MCMV was not detectable by day 100, Although all MCMV-i
nfected mice developed acute sialadenitis by day 28, a chronic (>100 days),
severe salivary gland inflammation and anti-Re and anti-La antibodies deve
loped only in the B6-lpr/lpr mice. Apoptotic cells were detected during the
acute, but not the chronic, phase of inflammation.
Conclusion. Both Fas- and TNFRI-mediated apoptosis contribute to the cleara
nce of MCMV-infected cells in the salivary glands. However, because Fas-med
iated apoptosis is necessary for the downmodulation of the immune response,
a defect in this process can lead to a postinfection, chronic inflammatory
response that resembles Sjogren's syndrome.