D. Hildeman et al., VACCINATION AGAINST PERSISTENT VIRAL-INFECTION EXACERBATES CD4(-CELL-MEDIATED IMMUNOPATHOLOGICAL DISEASE() T), Journal of virology, 71(12), 1997, pp. 9672-9678
Lymphocytic choriomeningitis virus (LCMV) infection of normal mice res
ults in a fatal immunopathologic meningitis mediated by CD8(+) cytotox
ic T lymphocytes (CTL). We have previously shown that female beta(2)-m
icroglobulin-deficient (beta(2)m-/-) mice, which are also deficient in
CD8(+) T cells, are susceptible to LCMV-induced immune-mediated menin
gitis, characterized by significant weight loss and mortality. This LC
MV disease in beta(2)m-/- mice is mediated by CD4(+) T lymphocytes. Ou
r previous studies have also demonstrated that male beta(2)m-/- mice a
re less susceptible than female beta(2)m-/- mice to LCMV-induced, immu
ne-mediated mortality and weight loss. In this report, we show that va
ccination of male beta(2)m-/- mice enhances immunopathology following
intracranial infection with LCMV. We observed increased production of
gamma interferon (IFN-gamma), an increase in CD4(+) CTL precursor freq
uency, and an increased frequency of IFN-gamma-producing cells from sp
leen cells of vaccinated male beta(2)m-/- mice. Vaccinated male beta(2
)m-/- mice also had significantly increased inflammation in the cerebr
ospinal fluid (CSF), characterized by a large CD4(+) T-cell infiltrate
. CSF cells from vaccinated mice showed increased production of IFN-ga
mma on day 7 postchallenge. Neither vaccinated nor control beta(2)m-/-
mice were able to clear virus, and the two groups had similarly high
levels of virus early after infection. These results suggest that the
magnitude of the early immune response is more important than the leve
l of virus in the brain in determining the outcome of immunopathology
in beta(2)m-/- mice. We show here that vaccination can increase CD4(+)
T-cell-dependent immunopathology to a persistent viral infection.