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

S. Stager, J. Alexander, A.C. Kirby, M. Botto, N. Van Rooijen, D.F. Smith, F. Brombacher, P.M. Kaye

Research output: Contribution to journalArticle

159 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1287-1292
Number of pages6
JournalNature Medicine
Volume9
DOIs
Publication statusPublished - 2003

Keywords

  • t cell responses
  • vaccine-induced CD8+
  • endogenous adjuvants

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