title: Ephrin B2 induces T cell costimulation.
abstract: Eph kinases form the largest family of receptor tyrosine kinases, and their ligands are ephrins (EFNs), which are cell surface proteins. Some Eph kinases and EFNs are expressed on T cells, B cells, and dendritic cells, but their functions in the immune system are largely unknown. In this study, we investigated the effect of EFNB2 on murine T cells. EFNB2 mRNA was expressed in the cortex of the thymus and white pulp of the spleen. At the protein level, it was expressed on T cells and monocytes/macrophages, but not on B cells. EFNB2Rs were expressed mainly on T cells. Solid-phase EFNB2 along with suboptimal anti-CD3 strongly stimulated T cell proliferation, with concomitant augmentation of IFN-gamma but not IL-2 or IL-4 secretion. The activity of cytotoxic T cells was also significantly enhanced in the presence of solid-phase EFNB2. These results indicate that EFNB2R cross-linking results in costimulation of T cells. EFNB2Rs were normally scattered on the T cell surface; after TCR cross-linking, they rapidly congregated to capped TCR complexes and then to patched rafts. This provides a morphological base for EFNB2Rs to participate in T cell costimulation. We also demonstrated that EFNB2R signaling led to augmented p38 and p44/42 mitogen-activated protein kinase activation. Our study shows that EFNB2 plays important roles in immune regulation.
authors.affiliation: Laboratory of Immunology and. Nephrology Service, Notre Dame Hospital, Centre Hospitalier de l'Université de Montréal, Université de Montréal, Montreal, Canada.
authors.forename: Guang
authors.initials: G
authors.lastname: Yu
authors.forename: Hongyu
authors.initials: H
authors.lastname: Luo
authors.forename: Yulian
authors.initials: Y
authors.lastname: Wu
authors.forename: Jiangping
authors.initials: J
authors.lastname: Wu
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000201:enzymology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D036388:Ephrin-B2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005434:Flow Cytometry; D007106:Immune Sera / Q000494:pharmacology; D017403:In Situ Hybridization; D008213:Lymphocyte Activation / Q000502:physiology*; D008222:Lymphokines / Q000096:biosynthesis; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism; D036183:Receptor, EphB2 / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D036388:Ephrin-B2; D007106:Immune Sera; D008222:Lymphokines; D036183:Receptor, EphB2