Nature Medicine
9, 1287 - 1292 (2003)
Published online: 21 September 2003; | doi:10.1038/nm933
Natural antibodies and complement are endogenous adjuvants for vaccine-induced CD8+ T-cell responsesSimona Stäger1, James Alexander2, Alun C Kirby1, Marina Botto3, Nico Van Rooijen4, Deborah F Smith5, Frank Brombacher6
& Paul M Kaye11
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E7HT, UK. 2
Department of Immunology, Strathclyde Institute for Biomedical Sciences, University of Strathclyde, Taylor Street, Glasgow, G4 ONR,UK. 3
Rheumatology Section, Faculty of Medicine, Imperial College London, Du Cane Road, London, W12 0NN, UK. 4
Department of Molecular Cell Biology, Vrije Universiteit, Amsterdam, 1081 B5, The Netherlands. 5
Wellcome Trust Laboratories for Molecular Parasitology, Department of Biological Sciences, Imperial College London, Exhibition Road, London, SW7 2AZ, UK. 6
Department of Immunology, University of Cape Town Medical School, Groote Schuur Hospital, 7925 Cape Town, South Africa.
Correspondence should be addressed to Paul M Kaye paul.kaye@lshtm.ac.ukCD8+ T cells are essential for long-term, vaccine-induced resistance against intracellular pathogens. Here we show that natural antibodies, acting in concert with complement, are endogenous adjuvants for the generation of protective CD8+ T cells after vaccination against visceral leishmaniasis. IL-4 was crucial for the priming of vaccine-specific CD8+ T cells, and we defined the primary source of IL-4 as a CD11b+CD11clo phagocyte. IL-4 secretion was not observed in antibody-deficient mice and could be reconstituted with serum from normal, but not Btk immune-deficient, mice. Similarly, no IL-4 response or CD8+ T-cell priming was seen in C1qa-/- mice. These results identify a new pathway by which immune complex−mediated complement activation can regulate T-cell-mediated immunity. We propose that this function of natural antibodies could be exploited when developing new vaccines for infectious diseases.
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