In addition to EAE, experimental autoimmune uveitis (EAU), a widely used animal model of human uveitis, is another CD4+ T-cell mediated organ-specific autoimmune disease which can be inhibited by agonistic anti-CD137 treatment (Shao et al., 2005). Uveitis is a common cause of human visual disability and blindness. EAU can be induced in susceptible rodent strains by immunization with retinal proteins such as the receptor retinoid binding protein (IRBP) (Donoso et al., 1989; Gery etal., 1986), retinal S antigen (S-Ag) (Wacker etal., 1977) andmelanin-associated Ag (MAA) (Bora etal., 1995; Broekhuyse etal., 1992) or by the adoptive transfer ofuveitogenic T cells to syngeneic rodents. TH 1-like response promotes the development of EAU (Tarrant et al., 1998), whereas TH2-like response manifests protective function (Rizzo etal., 1999; Wildner and Thurau, 1995), suggesting the Th1 nature of this type of autoimmune disease.
Similar as in EAE model, Shao and colleagues (Shao et al., 2005) observed that administration of agonistic anti-CD137 (2A) on the day of immunization prevented actively induced EUA in B10RIII mice by subcutaneous immmunization with 100 |g of IRBP161-180 peptide emulsified in an equal volume of CFA containing 500 |g/ml Mycobacterium tuberculosis H37 RA. T cells from 2A-treated mice showed deficit response to IRBP161-180 restimulation ex vivo and failed to transfer disease to naive syngeneic B10RIII mice. If anti-CD137 treatment was given six or twelve days after immunization, it did not protect against EAU. Such treatment did not affect adoptively transferred uveitis which was directly induced by activated IRBP peptide-specific T cells. These studies further support the idea that CD137 engagement inhibited CD4+ T cell-mediated autoimmune disease in the early stages of autoreactive T cell priming instead of the effector phases.
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