Ml. Krakowski et T. Owens, THE CENTRAL-NERVOUS-SYSTEM ENVIRONMENT CONTROLS EFFECTOR CD4(-CELL CYTOKINE PROFILE IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS() T), European Journal of Immunology, 27(11), 1997, pp. 2840-2847
In experimental allergic encephalomyelitis (EAE), CD4(+) T cells infil
trate the central nervous system (CNS). We derived CD4(+) T cell lines
from SJL/J mice that were specific for encephalitogenic myelin basic
protein (MBP) peptides and produced both Th1 and Th2 cytokines. These
lines transferred EAE to naive mice. Peptide-specific cells re-isolate
d from the CNS only produced Th1 cytokines, whereas T cells in the lym
ph nodes produced both Th1 and Th2 cytokines. Mononuclear cells isolat
ed from the CNS, the majority of which were microglia, presented antig
en to and stimulated MBP-specific T cell lines in vitro. Although CNS
antigen-presenting cells (APC) supported increased production of inter
feron (IFN)-gamma mRNA by these T cells, there was no increase in the
interleukin (IL)-4 signal, whereas splenic APC induced increases in bo
th IFN-gamma and IL-4. mRNA for IL-12 (p40 subunit) was up-regulated i
n both infiltrating macrophages and resident microglia from mice with
EAE. We have thus shown that a Th1 cytokine bias within the CNS can be
induced by CNS APC, and that IL-12 is up-regulated in microglial cell
s within the CNS of mice with EAE. Microglia may therefore control Th1
cytokine responses within the CNS.