May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Tolerance Does Develop in Transgenic Mice Expressing a Foreign Antigen Under Control of the Rhodopsin Promoter
D.I. Ham; S.J. Kim; J. Chen; B.P. Vistica; R.N. Fariss; R.S. Lee; E.F. Wawrousek; I. Gery
Author Affiliations & Notes
  • D.I. Ham
    Laboratory Immunology, National Eye Institute, NIH, Bethesda, MD, United States
  • S.J. Kim
    Laboratory Immunology, National Eye Institute, NIH, Bethesda, MD, United States
  • J. Chen
    Laboratory Immunology, National Eye Institute, NIH, Bethesda, MD, United States
  • B.P. Vistica
    Laboratory Immunology, National Eye Institute, NIH, Bethesda, MD, United States
  • R.N. Fariss
    Laboratory Immunology, National Eye Institute, NIH, Bethesda, MD, United States
  • R.S. Lee
    Laboratory Immunology, National Eye Institute, NIH, Bethesda, MD, United States
  • E.F. Wawrousek
    Laboratory Immunology, National Eye Institute, NIH, Bethesda, MD, United States
  • I. Gery
    Laboratory Immunology, National Eye Institute, NIH, Bethesda, MD, United States
  • Footnotes
    Commercial Relationships  D.I. Ham, None; S.J. Kim, None; J. Chen, None; B.P. Vistica, None; R.N. Fariss, None; R.S. Lee, None; E.F. Wawrousek, None; I. Gery, None.
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 991. doi:
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      D.I. Ham, S.J. Kim, J. Chen, B.P. Vistica, R.N. Fariss, R.S. Lee, E.F. Wawrousek, I. Gery; Tolerance Does Develop in Transgenic Mice Expressing a Foreign Antigen Under Control of the Rhodopsin Promoter . Invest. Ophthalmol. Vis. Sci. 2003;44(13):991.

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Abstract

Abstract: : Purpose: Data of recent studies indicated that transgenic (Tg) expression of foreign antigens (beta-gal; ovalbumin) in mouse retinae does not induce tolerance to these antigens. The present study examined the immune response/tolerance in Tg mice expressing in the retina another antigen, hen egg lysozyme (HEL). Methods: A Tg mouse line expressing HEL under control of the rhodopsin promoter ("rhoHEL-Tg") was generated by conventional techniques. HEL was detected in the retina of these mice by immunohistochemistry. Development of immunity or tolerance was determined by immunizing these Tg mice and their wild type controls with HEL in CFA and testing their lymphocyte proliferation and antibody responses 14 days later. Double-Tg mice were generated by mating the rhoHEL-Tg mice with Tg mice expressing HEL-specific TCR on most of their T-cells ("3A9" mice). Lymphocyte populations were identified and quantified by flow cytometry, while apoptosis in the mouse thymi was visualized by the TUNEL assay. Ocular changes were examined by routine histology. Results: rhoHEL-Tg mice developed immunotolerance to HEL, demonstrated by reduced cellular and humoral immune responses following immunization with HEL. Also, no inflammation was detected in eyes of the rhoHEL-Tg mice following immunization with HEL, whereas severe inflammation was seen in these Tg mice following adoptive transfer of activated HEL-specific T-cells from 3A9 donors. The development of central tolerance in rhoHEL-Tg mice was further indicated by the following observations in the (3A9 x rhoHEL-Tg) double-Tg mice: (i) marked reduction in the population of single positive (CD4) thymocytes; (ii) profound decrease in the populations of T-cells expressing the HEL-specific 3A9 TCR in both the thymus and the periphery; (iii) a significant increase in the number of apoptotic cells in the medulla of thymi from the double-Tg mice, as compared to their single-Tg 3A9 controls. Conclusions: Transgenic expression of HEL under control of the rhodopsin promoter induces highly effective central tolerance, probably due to thymic expression of HEL. Differences between this observation and previous studies could be attributed to the level of expression and/or immunological features of the antigens.

Keywords: uveitis-clinical/animal model • immunomodulation/immunoregulation • transgenics/knock-outs 
© 2003, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
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