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*
Center for Neurologic Diseases and
Laboratory of Immunogenetics and Transplantation, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115
We studied the kinetics of expression of costimulatory molecules
and cytokines in the central nervous system (CNS) in murine relapsing
experimental autoimmune encephalomyelitis (EAE). During the natural
course of EAE, B7-2 expression in the CNS correlated with clinical
signs, while B7-1 was exclusively expressed during remissions.
Interestingly, B7-1 was expressed on infiltrating mononuclear cells as
well as neuronal cells in the CNS. In the periphery, B7-1 expression on
APCs peaked with clinical disease but decreased on T cells. CD28 and
CTLA4 molecules, the two known ligands for B7-1 and B7-2, had distinct
expression patterns in the CNS; CD28 was highly expressed and
correlated with B7-2 expression on APCs (macrophages/microglia as well
as astrocytes) and with the clinical signs of EAE. CTLA4, on the other
hand, was expressed by substantially fewer cells during the effector
phase of disease and peaked during remission, which is consistent with
the emerging role of this molecule in the termination of immune
responses. The expression of CD40 and CD40L in the CNS was
increased during clinical attacks. The expression of IL-12, IFN-
,
and TNF-
correlated with disease activity and severity, while
TGF-ß was the only factor that was up-regulated during the recovery
phase. Interestingly, TGF-ß was also expressed by neurons during
remission. This is the first study demonstrating the kinetics of the in
vivo expression of costimulatory molecules, their ligands, and
cytokines in an autoimmune disease model characterized by remissions
and relapses. Our data suggest that the targeting of costimulatory
molecules to block an immune response must take into account the
expression patterns in the target organ.
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