Adjuvant effect of γ‐inulin is mediated by C3 fragments deposited on antigen‐presenting cells

The adjuvant effect of γ‐inulin, a strong activator of the alternative complement pathway, is well‐known, but its exact mechanism is not revealed yet. Here, we show that macrophages, isolated from the peritoneal cavity of γ‐inulin‐injected mice and used as antigen‐presenting cells, enhance the proliferation of antigen‐specific T‐cells up to 2.5‐fold when compared with macrophages of nontreated animals. This effect is abrogated by the presence of anti‐C3 F(ab′) 2 fragments and by prior decomplementation of the donor animals with CVF. It is demonstrated that treatment of mice with the adjuvant results in deposition of C3‐fragments onto the surface of peritoneal macrophages, as does in vitro incubation of the cells with γ‐inulin in the presence of fresh autologous serum. Prior incubation of macrophages with γ‐inulin plus serum in vitro enhances subsequent C3 production. Because it has been shown earlier that CR1/2 expressed on activated T‐cells and interacting with covalently bound C3‐fragments plays an important role in the augmentation of the adaptive response, our present results reveal a mechanism that contributes to the adjuvant effect of γ‐inulin and point to a further link between innate and adaptive immunity.