Apoptotic cells protect mice from autoimmune inflammation by the induction of regulatory B cells

M Gray, K Miles, D Salter, D Gray, J Savill

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)14080-5
Number of pages6
JournalProceedings of the National Academy of Sciences (PNAS)
Issue number35
Publication statusPublished - 2007


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