New perspectives on effector mechanisms in uveitis

Abstract

Experimental autoimmune uveitis (EAU) in its several variants represents human autoimmune uveitis and has been instrumental in obtaining insights into the basic mechanisms of disease. Studies have uncovered that in addition to CD4+ Th1 cells, uveitis can be induced also by CD8+ T cells. Antibodies may have a secondary role after the blood-retinal barrier has been broken. The role in uveitis of a recently discovered IL-17-producing effector T cell type, Th17, is being intensively studied. Th17 cells elicit EAU, can be found in uveitic eyes along with Th1 cells, and are dominant in some types of EAU. In other types of EAU, Th1 cells have a dominant role. The dominant effector type is at least in part determined by conditions under which initial exposure to self-antigen occurs. These findings shed light on the heterogeneity of human disease and may ultimately help to develop better and more rational treatment strategies for human uveitis.

Fig. 1

Effector T cell lineages. Based on information from published literature

Fig. 2

Th17 cells as well as Th1 cells infiltrate uveitic eyes. Eyes were obtained at peak of disease from C57BL/6 and B10.RIII mice immunized for EAU. The ocular tissues were dispersed chemically and enzymatically, and the cells were analyzed for phenotype and for intracellular cytokine expression after a brief incubation with PMA/Ionomycin and Brefeldin A [20]

Fig. 3

EAU can be induced by Th17 or by Th1 cells. B10.RIII mice received adoptive transfer of IRBP-specific cells from a polarized Th1 cell line unable to produce IL-17 or of cells from IFN-γ KO mice polarized toward the Th17 [20]. Eyes were collected at the peak of disease, processed for histopathology, and stained with hematoxylin and eosin. Note the neutrophilic infiltrate associated with Th17-induced EAU, consistent with its characteristic to recruit granulocytes