Abstract
Purpose: :
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 IFA or CFA. 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 generate 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 absenceof antigen stimulation. Increased expansion of both types of Th17 cells is seen in mice immunized with IRBP1-20/CFA, but not with IRBP1-20/IFA. Both T cell types produce IL-17, IL-22, and IFN-γ, but only bystander Th17 cells produce IL-10. Addition to culture medium with 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 neutralize the pathogenic activity of the IRBP-Th17 cells.
Conclusions: :
Immunized mice generate two functionally antagonistic types of IL-17+ T cells. 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.
Keywords: uveitis-clinical/animal model • autoimmune disease • inflammation