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(+)CD11c(lo) 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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adjuvants, Immunologic*
-
Animals
-
Antibodies / immunology*
-
Antigens, Protozoan / genetics
-
Antigens, Protozoan / metabolism
-
CD11b Antigen / immunology
-
CD11c Antigen / immunology
-
CD8-Positive T-Lymphocytes / immunology*
-
CD8-Positive T-Lymphocytes / metabolism
-
Complement Activation
-
Complement System Proteins / genetics
-
Complement System Proteins / immunology*
-
Interleukin-12 / metabolism
-
Interleukin-4 / genetics
-
Interleukin-4 / immunology
-
Interleukin-4 / metabolism
-
Leishmaniasis, Visceral / immunology
-
Leishmaniasis, Visceral / prevention & control
-
Mice
-
Mice, Inbred Strains
-
Mice, Knockout
-
Phagocytes / immunology
-
Phagocytes / metabolism
-
Protozoan Proteins / genetics
-
Protozoan Proteins / metabolism
-
Vaccines / immunology*
Substances
-
Adjuvants, Immunologic
-
Antibodies
-
Antigens, Protozoan
-
CD11b Antigen
-
CD11c Antigen
-
HASPB protein, Leishmania
-
Protozoan Proteins
-
Vaccines
-
Interleukin-12
-
Interleukin-4
-
Complement System Proteins