Characterization of T cells and cytokines in the aqueous humour (AH) in patients with Fuchs' heterochromic cyclitis (FHC) and idiopathic anterior uveitis (IAU)

Abstract

FHC and IAU are two forms of anterior uveitis which are localized to the eyes with no evidence of systemic involvement. However, FHC has distinct clinical features and differs from IAU in that the inflammation is low grade, steroid non-responsive, and has a less aggressive clinical course. To try to dissect the mechanism for this difference the phenotypes of the cells in the AH and blood (PB) and the cytokines present in the AH in patients with FHC and IAU were compared. Three-colour flow cytometry was performed on the cells isolated from the AH and PB. Percentage of cells bearing the following markers were determined: CD3, CD4, CD8, CD4/CD25, CD8/CD25, CD19 and CD14. The cytokines IL-4, IL-10, IL-12 and interferon-gamma (IFN-gamma) were assayed by ELISA. In both groups T cell numbers were higher in the AH than PB, although the distribution of T cell subsets in PB was similar. In the AH, CD8+ T cell numbers were higher in FHC than in IAU (P = 0.003), whilst CD4+ numbers were higher in IAU than FHC (P = 0.01). AH cytokine profiles were different in the two groups: IFN-gamma levels were higher and IL-12 levels lower in the FHC group than IAU (P = 0.02), whilst IL-10 levels tended to be higher in the FHC group (P = 0.5). We suggest that different local mechanisms governing the balance of T cell/cytokine-mediated inflammation in the anterior segment may underlie clinical differences such as chronicity and response to steroids in these disorders.

Cytokines and Chemokines in Uveitis - Is there a Correlation with Clinical Phenotype?

“…180 Vitreous humor-derived T-cell lines from FHC patients have shown increased IFN-γ and IL-10 production with low levels of IL-2 and no IL-4 as compared to peripheral blood-derived T cell lines from the same patients. 90 Additionally, IL-10 was significantly increased and IL-2 significantly decreased in comparison with the vitreous humor-derived T-cell lines from patients with idiopathic intermediate uveitis, which may be consistent with the less aggressive clinical course seen with FHC. A significantly higher percentage of CD4 + T cells were also present in the T-cell lines derived from patients with idiopathic uveitis as compared to those with FHC.…”

“…86 Elevated serum TNF-α levels seem to be positively correlated with recurrent episodes of uveitis of idiopathic origin. 88 Significantly increased levels of IFN-γ have also been detected in the aqueous humor of patients with chronic idiopathic anterior uveitis, 89 in the aqueous humor from patients with intermediate idiopathic uveitis in association with a significantly increased CD4 + population as compared to FHC, 90 in vitreous humor-derived T cell lines from patients with idiopathic intermediate uveitis, 91 and in the choroid of patients with idiopathic uveitis. 85 Raised MHC class I and II expression in iris biopsies was additionally noted in one study in conjunction with raised aqueous humor IFN-γ in idiopathic anterior uveitis.…”

Role of cytokines in the pathogenesis of endogenous uveitis

“…S jedne strane, smatra se da on ima važnu proinflamatornu ulogu i ponekad se koristi kao marker za praćenje progresije oboljenja (8). U skladu sa tim je nalaz da je koncentracija iFn-γ najviša pri maksimumu inflamacije tokom eaU (18), a detektovan je i povišen nivo iFn-γ u očnoj vodici osoba sa idiopatskim uveitisom (33,64). Pokazano je da iFn-γ dovodi do povećane ekspresije MHC molekula ii klase na ćelijama irisa, cilijarnog epitela i na retinalnim epitelnim pigmentnim ćelijama (65) i smatra se da je upravo ta ushodna regulacija značajna za patogenezu endogenih uveitisa (18).…”

A Suggestive Association of Fuchs Heterochromic Cyclitis with Cytotoxic T Cell Antigen 4 Gene Polymorphism

“…The aetiology of FHC is still unknown, and several theories have been suggested including an immunological disorder, supported by the detection of increased levels of oligoclonal immunoglobulin G within the aqueous humour of FHC patients [3,4] . Furthermore, the aqueous humour contains an increased number of CD8+ T cells, but fewer CD4+ T cells and macrophages, as compared to patients suffering from idiopathic anterior uveitis [5] . Also ␥ -interferon and interleukin 10 were elevated in aqueous humour of FHC patients.…”