Regulatory T cells control uveoretinitis induced by pathogenic Th1 cells reacting to a specific retinal neoantigen

C Terrada, S Fisson, Y De Kozak… - The Journal of …, 2006 - journals.aai.org
C Terrada, S Fisson, Y De Kozak, M Kaddouri, P Lehoang, D Klatzmann, BL Salomon…
The Journal of Immunology, 2006journals.aai.org
In many clinical cases, uveitis develops secondary to an infection. This could result from
peripheral activation followed by ocular penetration and reactivation of T cells specific for
microbial Ags expressed in the retina. To gain insights into the pathophysiology of uveitis,
we developed a new mouse model based on stable retinal expression of influenza virus
hemagglutinin (HA) neoantigen by adeno-associated virus-mediated gene transfer. One
month thereafter, we adoptively transferred HA-specific T cells, which were activated in vitro …
Abstract
In many clinical cases, uveitis develops secondary to an infection. This could result from peripheral activation followed by ocular penetration and reactivation of T cells specific for microbial Ags expressed in the retina. To gain insights into the pathophysiology of uveitis, we developed a new mouse model based on stable retinal expression of influenza virus hemagglutinin (HA) neoantigen by adeno-associated virus-mediated gene transfer. One month thereafter, we adoptively transferred HA-specific T cells, which were activated in vitro or in vivo. Intraocular inflammation was clinically and histologically observed in all animals within 15 days. The ocular infiltrate was composed mostly of macrophages and HA-specific T cells with a proinflammatory cytokine profile. Depletion of CD4+ CD25+ regulatory T cells exacerbated the disease, whereas HA-specific CD4+ CD25+ T cells given iv controlled the disease. This novel model should allow to better study the pathophysiology and therapeutic of uveitis.
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