Natural antibodies and complement are endogenous adjuvants for vaccine-induced CD8+ T-cell responses.
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.
D000276:Adjuvants, Immunologic; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003167:Complement Activation; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D014612:Vaccines / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000906:Antibodies; D000953:Antigens, Protozoan; D039481:CD11b Antigen; D039521:CD11c Antigen; C401884:HASPB protein, Leishmania; D015800:Protozoan Proteins; D014612:Vaccines; D018664:Interleukin-12; D015847:Interleukin-4; D003165:Complement System Proteins