CD4+Foxp3+ T-Regulatory Cells in Noninfectious Uveitis

Treatment of Uveitis by In Situ Administration of Ex Vivo–Activated Polyclonal Regulatory T Cells

“…Alternative treatments have to be proposed when all current therapeutic options have failed. Treg cell therapy is able to control uveitis in mice, as shown in this study and in other studies (13, 39, 40, 42), and a Treg cell deficiency has been reported in patients (49)(50)(51)(52). On the basis of our data, we have initiated a phase I/IIa clinical trial (http://ichgcp.net/clinical-trials-registry/NCT02494492) to test the feasibility and safety of intravitreous injection of autologous preactivated poly-Treg cells in patients suffering from severe bilateral noninfectious uveitis.…”

“…Tolerance to autoantigens expressed in the eye is broken during uveitis, even though the tissue contains substantial amounts of Treg cells, at least in mouse models [our work and the one of others (48)]. Their inability to control the disease may be due to their quantitative or functional defect in this inflammatory environment, as shown in mice (47), or in patients during the active phase of uveitis (49)(50)(51)(52). In this study, uveitis control by injected Treg cells was probably not due to an increase of whole Treg cell numbers in the eye, which was minor, but rather to a better efficacy of donor compared with recipient Treg cells.…”

Current concepts and future directions in the pathogenesis and treatment of non-infectious intraocular inflammation

“…In man, nTreg percentages in Behçet's disease patients with ocular complications are decreased before an ocular attack. 13,14 In Vogt Koyanagi Harada (VKH) syndrome, nTreg cells are similarly depleted and also less functional in their suppressive ability, and therefore overall loss of nTregs in active uveitis may contribute to patients' disease susceptibility and severity. 14,15 Immune regulation may not require antigen specificity, as in experimental models of uveitis (EAU), non-retinal antigen-specific nTregs can functionally suppress disease.…”

“…13,14 In Vogt Koyanagi Harada (VKH) syndrome, nTreg cells are similarly depleted and also less functional in their suppressive ability, and therefore overall loss of nTregs in active uveitis may contribute to patients' disease susceptibility and severity. 14,15 Immune regulation may not require antigen specificity, as in experimental models of uveitis (EAU), non-retinal antigen-specific nTregs can functionally suppress disease. Peripheral tolerance to retinal antigens is thought to be weak and likely to explain why peripheral antigen-specific T cells can be activated by ocular antigens or via autoantigen molecular mimicry during unrelated infection or inflammation and lead to induction of ocular inflammation.…”

Adalimumab specifically induces CD3+ CD4+ CD25high Foxp3+ CD127− T-regulatory cells and decreases vascular endothelial growth factor plasma levels in refractory immuno-mediated uveitis: a non-randomized pilot intervention study

“…Effects of anti-TNFa have already been described on CD4 cell numbers in sarcoidosis patients, 16 on the expression of IL-10 by CD4 T cells in posterior uveitis patients, 17 and on T-regulatory cells (Tregs) in RA and Crohn's patients. 18,19 This latter effect on Tregs might be of special clinical relevance in uveitis patients, as either a reduced frequency or impaired CD4 þ Foxp3 þ T-regulatory function has been described in noninfectious active uveitis, 20 active Behçet's disease, 21 and active VKH uveitis. 22 However, some discrepant results have been published that might be probably related to different Treg identification strategies.…”