title: [Functional studies of adhesion molecules on CD4-CD8- double negative T cells of autoimmune MRL/Mp-lpr/mice].
abstract: MRL/Mp-lpr/lpr (MRL-lpr) mice have been used for a model of human systemic lupus erythematosus. This strain of mice homozygous for an autosomal recessive mutation, lpr (lymphoproliferation), develops massive lymphadenopathy with the expansion of CD4-CD8- (double negative; DN) T cells. Recently it was demonstrated that lpr mice have defects in the gene of Fas antigen which mediates apoptosis, indicating a possibility of defect in negative selection of autoreactive T cells in the thymus of lpr mice. However, the mechanisms that control the accumulation of DN T cells in lymph nodes, and the involvement of DN T cells in the clinical manifestation of disease, have not been well understood. In this study, the expression of various cell adhesion molecules on lymphocytes from MRL-lpr mice was examined. The strong expression of CD44 antigen as well as heat stable antigen (HSA) on abnormal DN T cells of lymph nodes was characteristic in MRL-lpr mice. Furthermore, the accumulation of DN T cells in lymph nodes might result from augmented binding of lymphocytes to endothelial cell surface of lymph nodes, possibly due to the failure of Mel-14 antigen shedding from DN T cell surface. In addition, it was found that monoclonal antibodies reactive with cell adhesion molecules such as CD44, Mel-14, CD45R and HSA expressed on DN T cells, could trigger the lytic activity of DN T cells and redirected DN T cell-mediated lysis of Fc-receptor-positive target cells (EL-4). In contrast to T cell receptor (TCR)-mediated cytotoxicity, this redirected cytotoxicity was not inhibited by anti-lymphocyte function associated antigen-1 (LFA-1) antibody. Thus, cell adhesion molecules may play a major role in delivering the transmembrane signal to DN T cells of MRL-lpr mice that trigger the lytic activity. It is likely that DN T cells of MRL-lpr mice induce tissue damages by the interaction with ligand on vascular endothelium or extracellular matrix in vivo.
authors.affiliation: Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D015536:Down-Regulation; D004950:Esterases / Q000032:analysis; D066298:In Vitro Techniques; D008198:Lymph Nodes / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D015815:Cell Adhesion Molecules; D004950:Esterases; C022635:serine esterase