4.5 Article

Severe chronic experimental autoimmune uveitis (EAU) of the C57BL/6 mouse induced by adoptive transfer of IRBP1-20-specific T cells

Journal

EXPERIMENTAL EYE RESEARCH
Volume 82, Issue 2, Pages 323-331

Publisher

ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exer.2005.07.008

Keywords

autoimmunity; EAU; IRBP; T cell activation

Categories

Funding

  1. NEI NIH HHS [R01 EY014366, EY12974, EY014-366, R01 EY012974, EY14599] Funding Source: Medline
  2. CSR NIH HHS [RG3413A4] Funding Source: Medline

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Experimental autoimmune uveitis (EAU) can be induced in susceptible mice by immunization with retinal antigens. The response to uveitogens is genetically restricted. B10RIII and B10A mouse are highly susceptible to IRBP-induced uveitis. whereas B6 mouse is less susceptible. Immunization to B6 mouse with IRBP only induced very mild disease with low incidence. However, the susceptibility can be enhanced by transferring activated IRBP-specific T cells. In this study, we show that a reproducible and severe uveitis can be induced in B6 mice by adoptive transfer of IRBP-specific T cells. The disease incidence, severity, and duration can be readily controlled by the number and activation status of the injected T cells. Both CD4(+)- and CD8(+) IRBPI-20-specific T cells were identified in vitro IRBP peptide stimulation. In addition, IRBPI-20-specific T cells were consistently detected in recipient mice for up to 2 months, but only detected in the acute phase of the disease in actively immunized mice, indicating that persistency of injected IRBPI-20-specific T cells in recipient B6 mice might be one of the mechanisms causing chronic and severe disease. Giving that a large number of transgenic and KO mice are available in B6 background, an improved uveitis model in B6 mouse should assist the determination of pathogenesis of disease and identify molecules that can be targeted by new therapies. (c) 2005 Elsevier Ltd. All rights reserved.

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