Constitutively CD40-activated B cells regulate CD8 T cell inflammatory response by IL-10 induction

Pandelakis A. Koni, Anna Bolduc, Mayuko Takezaki, Yutetsu Ametani, Lei Huang, Jeffrey R. Lee, Stephen L. Nutt, Masahito Kamanaka, Richard A. Flavell, Andrew L. Mellor, Takeshi Tsubata, Michiko Shimoda

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

B cells are exposed to high levels of CD40 ligand (CD40L, CD154) in chronic inflammatory diseases. In addition, B cells expressing both CD40 and CD40L have been identified in human diseases such as autoimmune diseases and lymphoma. However, how such constitutively CD40-activated B cells under inflammation may impact on T cell response remains unknown. Using a mouse model in which B cells express a CD40L transgene (CD40LTg) and receive autocrine CD40/CD40L signaling, we show that CD40LTg B cells stimulated memory-like CD4 and CD8 T cells to express IL-10. This IL-10 expression by CD8 T cells was dependent on IFN-I and programmed cell death protein 1, and was critical for CD8 T cells to counterregulate their overactivation. Furthermore, adoptive transfer of naive CD8 T cells in RAG-1-/- mice normally induces colitis in association with IL-17 and IFN-γ cytokine production. Using this model, we show that adoptive cotransfer of CD40LTg B cells, but not wild-type B cells, significantly reduced IL-17 response and regulated colitis in association with IL-10 induction in CD8 T cells. Thus, B cells expressing CD40L can be a therapeutic goal to regulate inflammatory CD8 T cell response by IL-10 induction.

Original languageEnglish (US)
Pages (from-to)3189-3196
Number of pages8
JournalJournal of Immunology
Volume190
Issue number7
DOIs
StatePublished - Apr 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Koni, P. A., Bolduc, A., Takezaki, M., Ametani, Y., Huang, L., Lee, J. R., Nutt, S. L., Kamanaka, M., Flavell, R. A., Mellor, A. L., Tsubata, T., & Shimoda, M. (2013). Constitutively CD40-activated B cells regulate CD8 T cell inflammatory response by IL-10 induction. Journal of Immunology, 190(7), 3189-3196. https://doi.org/10.4049/jimmunol.1203364