Abstract
Abstract: :
Purpose: We have previously reported that CpG–ODN has a synergistic effect in the activation of uveitogenic T cells in Lewis rat. To determine whether a similar strategy will also be useful in mouse model, we have determined whether CpG–ODN could enhance the disease–inducing ability of uveitogenic peptide in B6 mice. Methods: Active uveitis was induced by immunizing with IRBP1–20 peptide with or without additional injection of CpG–ODN1826 in B6 mice. Adoptively transferred uveitis was induced by administration of IRBP–specific T cells that were primed in vivo and stimulated in vitro with immunizing peptide alone or peptide plus CpG–ODN1826. The disease incidence, severity and duration were followed after the induction of uveitis. Results: Adoptive transfer of IRBP1–20–specific T cells to naïve B6 mice consistently induced severer uveitis compared to milder uveitis induced by Ag immunization. Co–immunization to mice with small amount of CpG–ODN1826 enhanced the disease development. Significantly, in vitro activation and expansion of primed IRBP1–20–specific T cells was greatly augmented when supplemented with a small amount (1 µg/ml) of CpG–ODN1826. T cells co–stimulated by IRBP1–20 and CpG–ODN1826 consistently induced severer and persistent pathological disease. Conclusions:CpG–ODN could potentially trigger or exacerbate an autoimmune disease by mechanism(s) involving activation of autoreactive T cells, suggesting the involvement of bacterial and viral infections in the pathogenesis of uveitis.
Keywords: immunomodulation/immunoregulation • inflammation • autoimmune disease