Stäger, S., Alexander, J., Kirby, A. C., Botto, M., Van Rooijen, N., Smith, D. F., Brombacher, F. and Kaye, P. M. (2003) Natural antibodies and complement are endogenous adjuvants for vaccine-induced CD8+ T-cell responses. Nature Medicine, 9 (10). pp. 1287-1292. ISSN 1078-8956
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.
|Institution:||The University of York|
|Academic Units:||The University of York > Biology (York)|
|Depositing User:||York RAE Import|
|Date Deposited:||16 Mar 2009 16:10|
|Last Modified:||16 Mar 2009 16:10|
|Publisher:||Nature Publishing Group|