Constitutively CD40-Activated B Cells Regulate CD8 T Cell Inflammatory Response by IL-10 Induction
- Author(s)
- Koni, PA; Bolduc, A; Takezaki, M; Ametani, Y; Huang, L; Lee, JR; Nutt, SL; Kamanaka, M; Flavell, RA; Mellor, AL; Tsubata, T; Shimoda, M;
- Details
- Publication Year 2013-04-01,Volume 190,Issue #7,Page 3189-3196
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- 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-gamma 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. The Journal of Immunology, 2013, 190: 3189-3196.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- EFFECTOR MEMORY CELLS; NF-KAPPA-B; CD40 LIGAND; AUTOIMMUNE-DISEASE; SPONTANEOUS PROLIFERATION; IN-VIVO; EXPRESSION; LYMPHOCYTES; ACTIVATION; EXHAUSTION
- Research Division(s)
- Molecular Immunology
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608804/
- Publisher's Version
- https://doi.org/10.4049/jimmunol.1203364
- Terms of Use/Rights Notice
- Copyright ©2013 by The American Association of Immunologists, Inc. All rights reserved
Creation Date: 2013-04-01 12:00:00