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Natural antibodies and complement are endogenous adjuvants for vaccine-induced CD8+ t cell responses

Stager, S. and Alexander, J. and Kirby, A.C. and Botto, M. and Van Rooijen, N. and Smith, D.F. and Brombacher, F. and Kaye, P.M. (2003) Natural antibodies and complement are endogenous adjuvants for vaccine-induced CD8+ t cell responses. Nature Medicine, 9. pp. 1287-1292. ISSN 1078-8956

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Abstract

CD8+ 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.