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

Simona Stäger, James Alexander, Alun C Kirby, Marina Botto, Nico Van Rooijen, Deborah F Smith, Frank Brombacher, Paul M Kaye

Research output: Contribution to journalArticlepeer-review


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
Issue number10
Publication statusPublished - 21 Sept 2003


  • Adjuvants, Immunologic
  • Animals
  • Antibodies
  • Antigens, CD11b
  • Antigens, CD11c
  • Antigens, Protozoan
  • CD8-Positive T-Lymphocytes
  • Complement Activation
  • Complement System Proteins
  • Interleukin-12
  • Interleukin-4
  • Leishmaniasis, Visceral
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Phagocytes
  • Protozoan Proteins
  • Vaccines

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