Abstract
Purpose: :
The course of EAU in the rat can be monophasic or relapsing, depending on the antigen peptide used for induction. Retinal S-Antigen peptide PDSAg induces monophasic, IRBP peptide R14 relapsing disease. Recently we described differences in gene and protein expression of PDSAg- and R14-specific T cell lines, including IFN-γ and IL-17. Here we investigate Th1 and Th17 cells among intraocular T cells of both specificities.
Methods: :
EAU was induced by immunization with PDSAg or R14 in CFA. Intraocular cells were collected at various time points and stimulated with antigen or ConA. After in vitro stimulation for 3 days cells were stained for TCRαβ, IL-17 and IFN-γ expression.
Results: :
Intracellular staining for IFN-γ and IL-17 revealed a major intraocular IFN-γ+ and a minor IL-17+ population, of the latter the majority of cells were IFN-γ/IL-17 double positive. In R14-induced EAU up to 50% IL-17+ cells were found only at onset of EAU, they decreased during the course of intraocular inflammation and did not increase at relapses. In PDSAg-induced disease IL-17+ and double positive cells increased to more than 20% when intraocular inflammation subsided. Numbers of IFN-γ+ cells remained stable during R14-induced EAU, but decreased during the course of PDSAg-mediated disease. During spontaneous relapses of R14-induced EAU most intraocular IFN-γ+ T cells were antigen-specific, while the majority of IL-17+ cells was Ag non-specific (ConA stimulation).
Conclusions: :
Intraocular T cells in rat EAU were IFN-γ+, IL-17+ and IFN-γ+IL-17+. Depending of the antigen-specificity of the autoimmune response the populations varied and IL-17+ and IFN-γ/IL-17 double positive cells appeared in the eye at different stages during disease, suggesting that IL-17+ cells in monophasic PDSAg-mediated EAU might have regulatory functions, while IL-17+ cells in R14-induced EAU might play a role in infiltration of specific T cells or unspecific inflammatory cells.
Keywords: uveitis-clinical/animal model • cytokines/chemokines • immunomodulation/immunoregulation