C5a promotes spontaneous differentiation of CD4⁺ T cells to Th17 cells via homeostatic proliferation. (A) Quantitative RT-PCR for C3 and IL-6 mRNA in the joints of RAG2^−/− mice 12 wk after transfer of SKG CD4⁺ T cells (n = 6). (B) 10⁶ C5aR^+/+ or C5aR^−/− SKG CD4⁺ T cells were transferred to C5aR^+/+ or C5aR^−/− RAG2^−/− mice. Joint scores were assessed every week in two independent experiments. Error bars are means ± SD. (C) 2 × 10⁶ C5aR^+/+ or C5aR^−/− SKG CD4⁺ T cells were transferred to C5aR^+/+ or C5aR^−/− RAG2^−/− mice. Intracellular cytokines in recipient splenic CD4⁺ T cells were stained on day 7 (numbers indicate percentages). One representative out of four independent experiments is shown. (D and E) Percentages of IL-17⁺ or IFN-γ⁺ cells among CD4⁺ T cells in C5aR^+/+ or C5aR^−/− RAG2^−/− mice (n = 4 each) after transfer of SKG (D) or BALB/c CD4⁺ T cells (E). (F) A model for the role of complement activation in Th17-mediated autoimmune arthritis. Horizontal bars in A, D, and E are the means.