title: Constitutively CD40-activated B cells regulate CD8 T cell inflammatory response by IL-10 induction.
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.
authors: Department of Medicine, Georgia Regents University, Augusta, GA 30912, USA.
authors: Pandelakis A
authors: PA
authors: Koni
authors: Anna
authors: A
authors: Bolduc
authors: Mayuko
authors: M
authors: Takezaki
authors: Yutetsu
authors: Y
authors: Ametani
authors: Lei
authors: L
authors: Huang
authors: Jeffrey R
authors: JR
authors: Lee
authors: Stephen L
authors: SL
authors: Nutt
authors: Masahito
authors: M
authors: Kamanaka
authors: Richard A
authors: RA
authors: Flavell
authors: Andrew L
authors: AL
authors: Mellor
authors: Takeshi
authors: T
authors: Tsubata
authors: Michiko
authors: M
authors: Shimoda
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D019898:Autocrine Communication / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D003092:Colitis / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D007156:Immunologic Memory; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000941:Antigens; D019013:CD40 Antigens; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D016753:Interleukin-10; D023201:CD40 Ligand; D053633:Receptor, Interferon alpha-beta