Characterization of phenotype and cytokine profiles of T cell lines derived from vitreous humour in ocular inflammation in man

Abstract

Intermediate uveitis (IU) and Fuchs' heterochromic cyclitis (FHC) are two chronic ocular inflammatory disorders. They differ considerably in ocular morbidity, which is higher in IU. T cell lines were derived from the vitreous humour (VH) and peripheral blood (PB) of 10 patients with IU and four patients with FHC. There was a predominance of CD8+ in all the lines. However, there was a significantly higher percentage of CD4+ T cells in the T cell lines derived from VH of IU (32.0 +/- 8.6%) compared with FHC patients (19. 2 +/- 8.9%) (P = 0.04). The VH-derived T cell lines (VDTC) produced significantly higher levels of IL-2, interferon-gamma (IFN-gamma) and IL-10, but not IL-4, compared with PB-derived T cell lines (PBDTC) in both entities. There was significantly higher IL-2 production by VDTC from IU when compared with FHC patients (1810 +/- 220 pg/ml versus 518 +/- 94 pg/ml; P = 0.009), which could account for the more aggressive clinical features of this condition. In contrast IL-10 production was significantly higher by the VDTC from FHC compared with IU patients. The high IL-10 production by T cells infiltrating VH of FHC patients could down-regulate the inflammatory responses, thereby contributing to the benign clinical course seen in these patients. The accumulation of T cells with differing cytokine profiles in the VH suggests an important role for these cytokines in the pathogenesis of these chronic uveitides.

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

“…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. 91 A positive correlation between IL-4 and IL-5 has also been demonstrated with IL-6 levels unchanged as compared to controls but significantly decreased as compared to patients with idiopathic uveitis. 13,14 In the aqueous humor of FHC uveitis patients, TGF-β2 has been detected at significantly lower levels than control groups.…”

“…79,95 In humans, IL-4 has only been detected in low levels and at levels not significantly different from controls in the aqueous humor and serum of patients with idiopathic uveitis. 86 91 A recent study also showed that there were no significant differences in aqueous humor IL-4 levels between anterior uveitis, panuveitis and control groups, but that IL-5 was significantly not detected in the panuveitis groups with idiopathic uveitis as compared to controls and those with idiopathic anterior uveitis. 14 A decrease in aqueous humor IL-10 has been demonstrated in conjunction with an increase in activated CD4 + T cells in anterior uveitis, which could partially explain why in acute anterior uveitis, the inflammation is more severe.…”

“…It is suggested that since the beneficial effect of steroids in the control of disease activity may be due to their capacity to increase the spontaneous expression of IL-10, the already raised IL-10 level in aqueous humor precludes further beneficial steroid effects. 91 The significantly decreased CD4 + T cell population in FHC could explain this steroid unresponsiveness as compared to idiopathic uveitis, as this T-cell subset is the predominant target of the corticosteroids. 91 The clonal nature and predominance of CD8 + T cells in the aqueous humor of patients with FHC is suggestive of an antigen-driven process with a possible viral initiating factor, 180 and indeed the discovery of persistent rubella antibodies and DNA in FHC has suggested that rubella virus could be a causal factor.…”

“…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.…”

Vitrectomy for juvenile uveitis: prognostic factors for the long-term functional outcome

“…4,5,[9][10][11][12][17][18][19] A possible explanation for these results could be the restoration of an immunological homeostasis by the mechanical removal of the vitreous body with captured autoreactive T cells and proinflammatory cytokines during PPV. 24,25 The replacement of the vitreous with aqueous humor and its numerous immunomodulatory factors after PPV may have an additional regulatory effect. 26 In contrast, the need for systemic steroids and immunomodulatory treatment showed no significant difference before and after PPV.…”