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Interaction of B7RP-1 with ICOS Negatively Regulates Antigen Presentation by B Cells

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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-γ 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.

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Authors and Affiliations

  1. Division of Nephrology, Kantonsspital, St. Gallen, Switzerland

    Patricia Wahl, Roland Schoop & Rudolf P. Wüthrich

  2. Amgen, Inc., Thousand Oaks, California

    Thomas P. Horan & Steven K. Yoshinaga

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  1. Patricia Wahl
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  2. Roland Schoop
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  3. Thomas P. Horan
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  5. Rudolf P. Wüthrich
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Correspondence to Rudolf P. Wüthrich.

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Wahl, P., Schoop, R., Horan, T.P. et al. Interaction of B7RP-1 with ICOS Negatively Regulates Antigen Presentation by B Cells. Inflammation 27, 191–200 (2003). https://doi.org/10.1023/A:1025032429697

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