OBJECTIVE To characterize antigen-specific and bystander IL-17+ T cells induced in immunized mice. METHODS C57BL/6 (B6) mice were immunized with the uveitogenic peptide IRBP₁₋₂₀ in either incomplete (IFA) or complete (CFA) Freund's adjuvant. In vivo-primed T cells were stimulated with syngeneic APCs, with or without the immunizing peptide, under polarizing conditions. Activated T cells were analyzed for expression and production of IL-17. RESULTS B6 mice immunized with the uveitogenic peptide IRBP₁₋₂₀ generated two types of IL-17+ T cell: one specific for the immunizing autoantigen (IRBP-Th17) and a much more abundant type (bystander-Th17) that is not reactive with the immunizing antigen. The bystander-Th17 can be demonstrated when in vivo-primed T cells are cultured in Th17-polarizing conditions in the absence of antigen stimulation. Increased expansion of both types of Th17 cells was seen in mice immunized with IRBP₁₋₂₀/CFA, but not with IRBP₁₋₂₀/IFA. Both T-cell types produced IL-17, IL-22, and IFN-γ, but only bystander Th17 cells produced IL-10. Addition to culture medium of IL-6 and TGF-β1 caused more activation of bystander-Th17 T cells than IRBP-Th17 cells. When adoptively transferred into syngeneic naïve mice, the bystander-Th17 cells neutralized the pathogenic activity of the IRBP-Th17 cells. CONCLUSIONS A procedure commonly used to induce autoimmune disease promotes two functionally antagonistic types of IL-17+ T cells, and the pathogenic type is restricted to the population that specifically responds to the immunizing autoantigen. Molecular components of the CFA, rather than the immunizing peptide, promote the generation of both types of IL-17+ T cells.