May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Different Thresholds for Autoimmune Disease Induction in Mice That Express a Neo-Self Antigen in Photoreceptor Cells versus Astrocytes
Author Affiliations & Notes
  • S. W. McPherson
    Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota
  • N. D. Heuss
    Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota
  • T. N. Sam
    Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota
  • D. S. Gregerson
    Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota
  • Footnotes
    Commercial Relationships  S.W. McPherson, None; N.D. Heuss, None; T.N. Sam, None; D.S. Gregerson, None.
  • Footnotes
    Support  NIH grants EY011542 and EY016376, Research to Prevent Blindness, MInnesota Lions Club
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1996. doi:https://doi.org/
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      S. W. McPherson, N. D. Heuss, T. N. Sam, D. S. Gregerson; Different Thresholds for Autoimmune Disease Induction in Mice That Express a Neo-Self Antigen in Photoreceptor Cells versus Astrocytes. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1996. doi: https://doi.org/.

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

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Abstract

Purpose: : Identifying and characterizing the interactions between naïve or resting, antigen-specific (Ag) CD4 T cells and cognate antigen expressed in neural cells is crucial to understanding both the induction of tolerance and autoimmune disease. Previously, we reported a limited recognition of photoreceptor cell (PC) Ag by resting CD8 T cells (McPherson, et al., Immuology, 110:386). Here, we wish to determine if naïve or resting MHC-class II restricted (CD4) T cells are capable of PC Ag recognition in the normal retina and if there is a difference in the immune response when the Ag is expressed in other cells of the central nervous system (CNS).

Methods: : In order to generate sufficient numbers of Ag-specific, naïve T cells, we created T cell receptor (TCR) transgenic (Tg) mice (TCRβgal) using the TCR from our β-gal-specific 3E9 CD4 T cell line. TCRβgal bone marrow or mature, naïve T cells were transferred into mice expressing β-gal in PC (arrβgal) or astrocytes (GFAPβgal) and the β-gal specific T cells were analyzed for evidence of Ag encounter. Induction of autoimmune disease by adoptive transfer of TCRβgal T cells or immunization with β-gal, in conjunction with cytokine and adjuvant treatments, was used to demonstrate in vivo Ag recognition and different thresholds of autoimmune disease induction.

Results: : TCRβgal T cells recovered from arrβgal, GFAPβgal, or control mice showed similar levels of engraftment, maintained a naïve phenotype, and were similarly capable of responding to β-gal. While double Tg TCRβgal x arrβgal and TCRβgal x GFAPβgal mice gave no spontaneous autoimmune disease in retina or brain, transfer of TCRβgal T cells along with strategies that perturbed either effector T cell activation, migration, or recirculation, or regulatory T cells resulted in tissue specific autoimmune disease in arrβgal and GFAPβgal mice, demonstrating in vivo recognition of antigen by TCRβgal T cells. However, incidence and severity of autoimmune disease was consistently greater in GFAPβgal mice.

Conclusions: : β-gal in photoreceptors and astrocytes can be recognized by Ag-specific CD4 T cells but enhanced disease in GFAPβgal mice suggests that the barriers to overcoming self-tolerance to any particular CNS antigen are cell or site specific. Compared to other neural cells, PC immune privilege is, in part, maintained by enhanced limitations on the ability of naïve CD4 T cells to access retinal antigens, and by peripheral induction of regulatory T cells based on encounter with retina-derived antigens.

Keywords: autoimmune disease • immune tolerance/privilege • immunomodulation/immunoregulation 
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