KINETICS OF EXPRESSION OF COSTIMULATORY MOLECULES AND THEIR LIGANDS IN MURINE RELAPSING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN-VIVO

We studied the kinetics of expression of costimulatory molecules and c ytokines in the central nervous system (CNS) in murine relapsing exper imental autoimmune encephalomyelitis (EAE). During the natural course of EAE, B7-2 expression in the CNS correlated with clinical signs, whi le B7-1 was exclusively expressed during remissions. Interestingly, B7 -1 was expressed on infiltrating mononuclear cells as well as neuronal cells in the CNS, Zn the periphery, B7-1 expression on APCs peaked wi th clinical disease but decreased on T cells. CD28 and CTLA4 molecules , the two known ligands for B7-1 and B7-2, had distinct expression pat terns in the CNS; CD28 was highly expressed and correlated with B7-2 e xpression on APCs (macrophages/microglia as web as astrocytes) and wit h the clinical signs of EAE. CTLA4, on the other hand, was expressed b y substantially fewer cells during the effector phase of disease and p eaked during remission, which is consistent with the emerging role of this molecule in the termination of immune responses. The expression o f CD40 and CD40L in the CNS was increased during clinical attacks. The expression of IL-12, IFN-gamma, and TNF-alpha correlated with disease activity and severity, while TGF-beta was the only factor that was up -regulated during the recovery phase. interestingly, TGF-beta was also expressed by neurons during remission. This is the first study demons trating the kinetics of the in vivo expression of costimulatory molecu les, their ligands, and cytokines in an autoimmune disease model chara cterized by remissions and relapses. Our data suggest that the targeti ng of costimulatory molecules to block an immune response must take in to account the expression patterns in the target organ.