The role of class II MHC (la) antigen and homing/adhesion molecule expression on cerebrovascular endothelial cells (EC) in the model autoimmune disease, experimental allergic encephalomyelitis (EAE), in SJL/J mice, is indicated by several independent observations. These include concomitant expression of these antigens with disease and inhibition of disease induction with specific antibody treatment. The mechanism of interferon-gamma (IFN)-induced expression of la antigen was studied in vitro in order to assess potential regulatory mechanisms. A variety of factors which modulate IFN-induced la antigen expression were studied. These include agonists and antagonists of adrenergic receptors (which are found on cerebrovascular EC); neurohormones (which are known to affect the course of EAE; and cytokines (which are released by encephalitogenic lymphocytes, as well as circulating macrophages). The results demonstrate that an interaction between at least two signal transduction pathways (protein kinase A and protein kinase C) plays a modulatory role in la antigen expression. In addition, cytokines released by encephalitogenic T-cells (i.e., TNF) and non-encephalitogenic T-cells (i e., TGF) inhibit la antigen expression. The expression of a lymphocyte adhesion molecule known as mala-2 is up-regulated by TNF and down-regulated by TGF. The actual degree of lymphocyte adhesion to TNF- or TGF-treated cells corroborates these findings. IFN-treatment of cerebral vascular EC isolated from human brain also resulted in the expression of class II MHC (HLA-DR and -DP) antigen expression. Only low levels of HLADQ antigen were observed.
