Lymphocytes migrate from blood into lymph nodes (LN) of rats specifically at segments of venules lined by high endothelium (HEV). We have previously shown that pretreatment of LN HEV cells with pro-inflammatory
cytokines such as tumour
necrosis factor-alpha (
TNF-alpha) and
interferon-gamma (IFN-gamma), augments their adhesiveness for thoracic duct lymphocytes (TDL). Here we report that a mouse
monoclonal antibody, 3C10, recognized tissue-specific endothelial determinants on rat LN HEV cells and blocked their adhesiveness for TDL and EL-4J cells transfected with rat
L-selectin. In contrast, 3C10 antibody did not inhibit lymphocyte attachment to Peyer's patch (PP) frozen sections or cultured PP HEV cells. The antibody immunoprecipitated from LN HEV cells two
proteins with apparent molecular weights of 90,000 and 50,000. The expression of 3C10
antigen on LN HEV cells was increased by incubation with
TNF-alpha or IFN-gamma. Furthermore, pretreatment of
cytokine-stimulated LN HEV cells with 3C10 antibody blocked TDL binding in a dose-dependent manner. In contrast, 3C10
antigen expression on LN HEV cells was significantly decreased following incubation of cells with
transforming growth factor-beta 1 (TGF-beta 1). In addition,
TGF-beta 1 also abrogated the adhesiveness of LN HEV cells stimulated with
TNF-alpha, IFN-gamma or both
cytokines. Together, these data suggest that endothelial determinants recognized by the 3C10 antibody are tissue-specific
ligands for lymphocyte adhesion and
cytokines such as
TNF-alpha and
TGF-beta differentially regulate their expression and function.