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 language | English |
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Pages (from-to) | 1287-1292 |
Number of pages | 6 |
Journal | Nature Medicine |
Volume | 9 |
Issue number | 10 |
DOIs | |
Publication status | Published - 21 Sept 2003 |
Keywords
- 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