Soluble Fas ligand and soluble Fas in ocular fluid of patients with uveitis

Abstract

Aims-To investigate the presence of soluble Fas ligand (sFasL) and soluble Fas (sFas) in ocular fluid of patients with uveitis. Methods-Samples of aqueous humour (AH, n=17), vitreous fluid (n=9), and serum (n=60) were collected from patients with uveitis which included Behçet's disease, Vogt-Koyanagi-Harada disease, sarcoidosis, human T lymphotropic virus type 1 (HTLV-I) uveitis, sympathetic ophthalmia, HLA-B27 associated acute anterior uveitis, and ocular toxoplasmosis. The AH of patients with age related cataract without uveitis obtained during cataract surgery was used as controls (n=20). The amounts of sFasL and sFas were measured by enzyme linked immunosorbent assay. Results-Significant amounts of sFasL were detected in AH of patients with age related cataract (non-uveitis group). sFasL was also detected in AH of patients with uveitis, though the amounts were slightly lower than those in the non-uveitis group. On the other hand, the levels of sFas in AH of patients with uveitis were significantly higher than those in controls. As for the disease activity, the levels of sFasL and sFas in the vitreous fluid of patients with active uveitis were significantly higher than those in inactive uveitis. sFasL in the serum of healthy donors and patients with uveitis was below detectable levels, except for patients with HTLV-I uveitis who had significant amounts of sFasL in the serum. The levels of sFas in the serum of patients with Behçet's disease, sarcoidosis, and HTLV-I uveitis were significantly higher than those of healthy donors. Conclusions-sFasL is present in the AH of non-uveitic eyes with age related cataract. Intraocular levels of sFasL and sFas are significantly increased in uveitis, particularly in active uveitis. These data suggest that intraocular sFasL and sFas may have a regulatory role in uveitis.

Inhibition of T Cell Apoptosis in the Aqueous Humor of Patients with Uveitis by IL-6/Soluble IL-6 Receptor trans-Signaling

“…In humans, functional mutations in the Fas gene leads to a range of autoimmune diseases, including uveitis (35). Previous reports have suggested that AqH from healthy subjects contains proapoptotic factors (36), and that Fas-induced apoptosis might be involved in the spontaneous resolution of inflammation observed in patients with acute anterior uveitis (13,15,16). The present report suggests that the ocular microenvironment in uveitis has no modulatory effect on Fas-induced apoptosis.…”

“…Many studies have focused on Fas-mediated apoptosis during intraocular inflammation (13)(14)(15)(16), but the failure of many cases of uveitis to resolve suggests that SFD-induced apoptosis may be diminished. T lymphocytes can be protected from SFD-induced apoptosis by members of the common ␥-chain cytokine family, including IL-2, IL-4, IL-7, IL-9, and IL-15 (17), and type I IFNs (18).…”

Immunopathology in ocular toxoplasmosis: facts and clues

“…However, these chemokines were not detected in the serum. Soluble FasL has also been detected in the aqueous humour of non-uveitic eyes with age-related cataracts (Sugita et al 2000). In organisms that are resistant to Fas-FasL, Fas-FasL and TRAIL are involved in tumour surveillance of the eye and may also contribute to the development of immune privilege in cases of infectious uveitis.…”

B7-H1-Induced Apoptosis as a Mechanism of Immune Privilege of Corneal Allografts

“…Anterior chamber-associated immune deviation (ACAID) 3 is a well-known phenomenon in which Ag-specific peripheral tolerance is induced after Ag injection into the anterior chamber (9,10). The anterior chamber contains biologically relevant concentrations of various immunomodulatory neuropeptides, growth factors, cytokines, and soluble cell surface receptors, such as ␣-melanocyte-stimulating hormone (11), vasoactive intestinal peptide (12), calcitonin gene-related peptide (13), TGF-␤ (14), thrombospondin (15), macrophage migration inhibitory factor (16), IL-1 receptor antagonist (17), CD46 (18), CD55 (18), CD59 (18), and CD95L (19). These factors suppress innate and adaptive immunity and maintain the immune suppressive microenvironment within the eye (11)(12)(13)(14)(15)(16)(17)(18)(19).…”