May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Alpha–melanocyte stimulating hormone (–MSH) induced regulatory T cells promote retinal allograft survival in the mouse eye
Author Affiliations & Notes
  • N. Kitaichi
    Schepens Eye Research Institute, Harvard Medical School, Boston, MA
  • T.F. Ng
    Schepens Eye Research Institute, Harvard Medical School, Boston, MA
  • M.J. Young
    Schepens Eye Research Institute, Harvard Medical School, Boston, MA
  • A.W. Taylor
    Schepens Eye Research Institute, Harvard Medical School, Boston, MA
  • Footnotes
    Commercial Relationships  N. Kitaichi, None; T.F. Ng, None; M.J. Young, None; A.W. Taylor, Schepens Eye Research Institute P.
  • Footnotes
    Support  NIH Grant EY107452, Massachusetts Lions Eye Research Fund, and JSPS Research Grant
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 2312. doi:
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      N. Kitaichi, T.F. Ng, M.J. Young, A.W. Taylor; Alpha–melanocyte stimulating hormone (–MSH) induced regulatory T cells promote retinal allograft survival in the mouse eye . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2312.

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

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Abstract

Abstract: : Purpose: We have demonstrated that the neuropeptide α–MSH mediates the induction of autoantigen–specific regulatory T (Treg) cells. The adoptive transfer of α–MSH–induced Treg cells specific to ocular autoantigens can suppress T cell activity that mediates experimental autoimmune uveoretinitis. These results suggest that α–MSH induced Treg cells can also suppress T cell responses that mediate graft rejection. Therefore, we examined the possibility that ocular autoantigen–specific, α–MSH–induced Treg cells can promote retinal grafts survival. Methods: Retinal tissue was collected from postnatal day 8 GFP transgenic C57BL/6J mice. The retinal tissue was injected into the vitreous cavity of allogenic 7 weeks old B10.RIII mice. On the same day of the retinal transplantation, interphotoreceptor retinoid–binding protein peptide (IRBPp) specific Treg cells were adoptively transferred (1x106cells) into grafted mice. We generated the Treg cells by treating IRBPp–primed T cells with α–MSH (30 pg/ml) and activating them with IRBPp–pulsed antigen presenting cells in vitro. The transplanted grafts were evaluated by fundus and histological examinations. Results: On day 12 after placing the retinal allografts into the vitreous, we observed 100% survival of the retinal allografts in mice injected with IRBPp–specific Treg cells. This is in contrast to only 25% surviving allografts in mice injected with OVA–specific Treg cells. Histological staining of the surviving retinal grafts revealed that bone marrow derived cells were found outside the graft in the mice injected with IRBPp specific Treg cells; whereas, the cells infiltrated the grafts in the mice not injected with IRPBp specific Treg cells. Conclusions: The ocular autoantigen–specific Treg cells induced with α–MSH promoted the survival of retinal allografts and may change the activity of intraocular immune cells to the allografts. Our results further demonstrate that we can use the mechanisms of aqueous humor immunosuppression to suppress alloimmunity, and promote graft survival and immune privilege.

Keywords: immunomodulation/immunoregulation • immune tolerance/privilege • transplantation 
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