May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Thymus–derived CD4+CD25+ regulatory T cells set the threshold of susceptibility to Experimental Autoimmune Uveitis (EAU)
Author Affiliations & Notes
  • R.S. Grajewski
    Laboratory of Immunology, National Eye Institute, Bethesda, MD
  • P.B. Silver
    Laboratory of Immunology, National Eye Institute, Bethesda, MD
  • R.K. Agarwal
    Laboratory of Immunology, National Eye Institute, Bethesda, MD
  • S.–B. Su
    Laboratory of Immunology, National Eye Institute, Bethesda, MD
  • C.–C. Chan
    Laboratory of Immunology, National Eye Institute, Bethesda, MD
  • R.R. Caspi
    Laboratory of Immunology, National Eye Institute, Bethesda, MD
  • Footnotes
    Commercial Relationships  R.S. Grajewski, None; P.B. Silver, None; R.K. Agarwal, None; S. Su, None; C. Chan, None; R.R. Caspi, None.
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 1007. doi:
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      R.S. Grajewski, P.B. Silver, R.K. Agarwal, S.–B. Su, C.–C. Chan, R.R. Caspi; Thymus–derived CD4+CD25+ regulatory T cells set the threshold of susceptibility to Experimental Autoimmune Uveitis (EAU) . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1007.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose:To investigate whether there is a role for thymically derived "natural" CD4+CD25+ regulatory T cells in setting the threshold of susceptibility to experimental autoimmune uveitis (EAU). Methods:EAU–susceptible B10.RIII mice were depleted of CD25+ cells by monoclonal antibody treatment, or were supplemented with purified CD4+CD25+ cells, and were immunized with a low–dose regimen of the retinal antigen IRBP. EAU scores and associated immunological responses were examined. Results:CD25–depleted mice had an earlier disease onset as well as enhanced disease incidence and severity compared to non–depleted controls (p<0.009). Thymic origin of the CD25+ cells was confirmed in adult–thymectomized mice, by delaying EAU challenge for 4 weeks after CD25+ cell depletion, so as to allow for regeneration of any non–thymically derived regulatory cells. Depleted mice exhibited higher DTH responses to IRBP, but in vitro antigen–specific proliferation and cytokine response patterns were unaltered. Conversely, mice supplemented with CD4+CD25+ T cells had reduced disease scores. To examine whether numbers of CD4+CD25+ T cells could explain strain–specific differences in EAU susceptibility, we compared numbers of CD4+CD25+ cells in naïve spleens and thymi of a series of mouse strains that vary in susceptibility to EAU (B10.RIII > B10.A > C57BL6 > DBA2 > BALB/c = AKR). There was no significant difference in the numbers of CD4+CD25+ regulatory T cells among the tested strains. Conclusions:Our data indicate that CD4+CD25+ regulatory T cells play an important role in setting the threshold of susceptibility to EAU, however, total numbers of CD4+CD25+ T cells cannot constitute a simple explanation for strain susceptibility differences in this model.

Keywords: uveitis–clinical/animal model • autoimmune disease 
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