Kl. Buchanan et Ha. Doyle, Requirement for CD4(+) T lymphocytes in host resistance against Cryptococcus neoformans in the central nervous system of immunized mice, INFEC IMMUN, 68(2), 2000, pp. 456-462
The importance of cell-mediated immunity (CMI) and CD4(+) T lymphocytes in
host resistance against Cryptococcus neoformans is well documented and is e
xemplified by the high susceptibility to progressive infection with this pa
thogen of AIDS patients with reduced CD4(+) T-cell numbers. Although much h
as been learned about the role of CMI in the clearance of C, neoformans fro
m the lungs and other internal organs, less is known about the protective m
echanisms in the brain, the organ most frequently involved with a fatal out
come of cryptococcosis, We hypothesized that host resistance mechanisms aga
inst C, neoformans in the central nervous system (CNS) were similar to thos
e outside the CNS (i.e., gamma interferon [IFN-gamma], CD4(+) T cells, and
others), To test this hypothesis, we used a murine model of cryptococcal me
ningitis whereby cryptococci are introduced directly into the CNS. In exper
iments where mice were immunized to mount an anticryptococcal CMI response,
our results indicate that immunization induced protective mechanisms that
could be detected in the CNS by inhibition of the growth of viable yeast ce
lls. Flow cytometric analyses of leukocytes in brain and spinal cord homoge
nates revealed that T lymphocytes, macrophages, and neutrophils accumulated
in C, neoformans-infected brains of immune mice. In vivo depletion of CD4(
+) T cells, but not CD8(+) T cells, resulted in significantly reduced leuko
cyte accumulation in the brains of immune mice. Furthermore, depletion of C
D4(+) T cells or neutralization of IFN-gamma exacerbated CNS infection in i
mmune mice, suggesting a critical role for CMI mechanisms in acquired prote
ction in the CNS.