Abstract
Purpose: :
The strict compartmentation of T cells in Th1, Th2 and Th17 was mitigated with the discovery of T cells that simultaneously produce IFN-γ and IL-17. They are found in chronically inflamed tissues and are not stable with respect to their cytokine expression. The role of these cells is still unknown. We have investigated intraocular T cells during the course of EAU with respect to their cytokine and Foxp3 expression in our rat model of monophasic and relapsing-remitting uveitis.
Methods: :
After induction of EAU with PDSAg (monophasic EAU) or R14 (relapsing EAU) in CFA we collected intraocular cells at various time points during ocular inflammation and stained them ex vivo for TCRαβ and intracellular IFN-γ, IL-17, IL-10 and Foxp3 expression.
Results: :
During the course of PDSAg-induced, monophasic uveitis intraocular T cell populations coexpressing IFN-γ and IL-17 increased from onset via peak to remission of EAU. IL-10+ and IL-17+/IL-10+ cells displayed a similar population dynamic, the latter increased to about 30% of the Th17 population at remission. Like Foxp3+ cells, IFN-γ+/IL-10+ cells were a minor population remaining stable during the course of monophasic EAU. In R14-induced relapsing EAU the number of IL-17+ and IFN-γ+/IL-17+ cells decreased at remission, while IFN-γ+ cell numbers remained elevated. IL-17+/IL-10+ cells decreased during remission of R14-induced EAU, while IFN-γ+/IL-10+ and Foxp3+ cells were also minor intraocular lymphocyte populations.
Conclusions: :
The change of the intraocular T cell populations during EAU, the large numbers of T cells producing multiple cytokines and the differences observed between monophasic and relapsing disease points to a strong population dynamics in the eye, potentially influencing the course of EAU. The strong increase of IL-10+ T cells in the eyes during monophasic EAU suggests a regulatory role of these cells with a potential to prevent relapses. Foxp3+ cells seem to play no role in preventing recurrent EAU.
Keywords: uveitis-clinical/animal model • cytokines/chemokines • immunomodulation/immunoregulation