Submitted June 20, 2008
Accepted January 12, 2009
C1q enhances IFN-
production by antigen specific T cells via the CD40 co-stimulatory pathway on dendritic cells
Paramita Baruah, Ingrid E. Dumitriu, Talat H. Malik, H Terence Cook, Julian Dyson, Diane Scott, Elizabeth Simpson, and Marina Botto*
Molecular Genetics and Rheumatology Section, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom
Department of Histopathology, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom
Department of Immunology, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom
* Corresponding author; email: m.botto{at}imperial.ac.uk.
Dendritic cells (DCs) are known to produce C1q the initiator of the classical complement pathway. We demonstrate that murine DCs deficient in C1q (C1qa-/-) are poorer than wild-type (WT) DCs at eliciting the proliferation and Th-1 differentiation of antigen specific T cells. These defects result from decreased production of IL-12p70 by C1qa-/- DCs and impaired expression of co-stimulatory molecules CD80 and CD86 in response to CD40 ligation. The defective production of IL-12p70 and the reduced expression of CD80 and CD86 by C1qa-/- DCs were specifically mediated via CD40 ligation, as normal levels of IL-12p70 and CD80/86 were observed following ligation of TLRs on C1qa-/- DCs. CD40 ligation on C1qa-/- DCs, but not TLR ligation, results in decreased phosphorylation of p38 and ERK1/2 kinases. A strong co-localisation of CD40 and C1q was observed by confocal microscopy upon CD40 ligation (but not TLR ligation) on DCs. Furthermore, human DCs from two C1q deficient patients were found to have impaired IL-12p70 production in response to CD40L stimulation. Our novel data suggest that C1q augments the production of IL-12p70 by mouse and human DCs following CD40 triggering and plays important roles in sustaining the maturation of DCs and guiding the activation of T cells.
