title: Interaction of B7RP-1 with ICOS negatively regulates antigen presentation by B cells.
abstract: Stimulation of T cells through the T cell receptor is insufficient for optimal T cell activation. A second activation signal is necessary, being usually provided by the costimulatory molecule CD28. Recently, additional costimulatory pathways have been identified, including inducible costimulator (ICOS) and its ligand B7RP-1. We have examined the role of the B7RP-1/ICOS costimulatory pathway on antigen presentation by B cells, using the I-Ak and I-Ek-positive CH27 B cell line and several different T cell lines. We found that CH27 expressed B7RP-1 and PD-L1 whereas the T cell lines expressed ICOS and PD-1. In the presence of HEL, the T cell hybridomas C10 and 3A9 released IL-2, which is indicative of antigen-specific T cell activation by the CH27 cells. Unexpectedly, blocking antibodies for B7RP-1 and ICOS enhanced the IL-2 response in both T cells. As expected, an increase in the production of IL-2 was seen when blocking antibodies for PD-1 were used. Blocking with antibodies for I-Ak, CD28, B7.1, and B7.2 lead to a decrease in IL-2 production. Additionally we tested a Th1 and a Th2 T cell clone. Blockade of B7RP-1/ICOS lead to an increased IFN-gamma response in Th1 cells (A.E7) and an increased IL-4 response in Th2 cells (D10.G4.1). Intracellular staining also showed an increase in cytokine production when the B7RP-1/ICOS pathway was blocked. In conclusion, the B7RP-1/ICOS pathway is negatively regulating T cell activation by B cells and may play a role similar to that of the PD-L1/PD-1 pathway.
authors.affiliation: Division of Nephrology, Kantonsspital, St. Gallen, Switzerland, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Wahl
authors.forename: Roland
authors.initials: R
authors.lastname: Schoop
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Horan
authors.forename: Steven K
authors.initials: SK
authors.lastname: Yoshinaga
authors.forename: Rudolf P
authors.initials: RP
authors.lastname: Wüthrich
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism* / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000276:immunology*; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D051379:Mice
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; C556694:Icos protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein