Apoptotic cells protect mice from autoimmune inflammation by the induction of regulatory B cells.
The maintenance of immune tolerance to apoptotic cells (AC) within an inflammatory milieu is vital to prevent autoimmunity. To investigate this, we administered syngeneic AC i.v. into mice carrying a cohort of ovalbumin (OVA)-specific transgenic T cells (DO11.10) along with OVA peptide and complete Freund's adjuvant, observing a dramatic increase in OVA-specific IL-10 secretion. Activated splenic B cells responded directly to AC, increasing secretion of IL-10, and this programming by AC was key to inducing T cell-derived IL-10. We went on to ask whether AC are able to modulate the course of autoimmune-mediated, chronic inflammation. AC given up to 1 month before the clinical onset of collagen-induced arthritis protected mice from severe joint inflammation and bone destruction. Antigen-specific CD4(+) T cells again secreted significantly more IL-10, associated with a reduced titer of pathogenic anti-collagen II antibodies. Inhibition of IL-10 in vivo reversed the beneficial effects of AC. Passive transfer of B cells from AC-treated mice provided significant protection from arthritis. These data demonstrate that AC exert a profound influence on an adaptive immune response through the generation of CD19(+) regulatory B cells, which in turn are able to influence the cytokine profile of antigen-specific effector T cells.
Gray
M
M
Medical Research Council Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom. mohini.gray@ed.ac.uk
Miles
K
K
Salter
D
D
Gray
D
D
Savill
J
J
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology* / Q000517:prevention & control; D016753:Interleukin-10 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D016753:Interleukin-10; D010047:Ovalbumin
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