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International Immunology Advance Access published online on July 19, 2005
International Immunology, doi:10.1093/intimm/dxh275
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Published by Oxford University Press for The Japanese Society for Immunology
Received July 13, 2004
Accepted April 27, 2005

Article

Thymic expression of peripheral tissue antigens in humans: a remarkable variability among individuals

Hiroshi Takase 1, Cheng-Rong Yu 2, Rashid M. Mahdi 2, Daniel C. Douek 3, Gregory B. DiRusso 4, Frank M. Midgley 4, Rajpreet Dogra 5, Gloria Allende 5, Eliot Rosenkranz 6, Alberto Pugliese 5, Charles E. Egwuagu 2, and Igal Gery 2*

1 National Eye Institute, NIH, Building 10, Room 10N112, Bethesda, MD 20892, USA; Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
2 National Eye Institute, NIH, Building 10, Room 10N112, Bethesda, MD 20892, USA
3 National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
4 Children's National Medical Center, Washington, DC 20010, USA
5 Immunogenetics Program, Diabetes Research Institute, University of Miami, Miami, FL 33136, USA
6 Division of Cardiothoracic Surgery, University of Miami, Miami, FL 33136, USA

* To whom correspondence should be addressed.
Igal Gery, E-mail: geryi{at}nei.nih.gov


  Abstract

The majority of maturing T lymphocytes that recognize self-antigens is eliminated in the thymus upon exposure to their target antigens. This physiological process of negative selection requires that tissue-specific antigens be expressed by thymic cells, a phenomenon that has been well studied in experimental animals. Here, we have examined the expression in human thymi of four retinal antigens, that are capable of inducing autoimmune ocular disease retinal S-antigen (S-Ag), recoverin, RPE65 and inter-photoreceptor retinoid-binding protein (IRBP)], as well as four melanocyte-specific antigens, two of which are used as targets for melanoma immunotherapy [gp100, melanoma antigen recognized by T cells 1, tyrosinase-related protein (TRP)-1 and TRP-2]. Using reverse transcription (RT)-PCR, we found that all thymic samples from the 18 donors expressed mRNA transcripts of most or all the eight tested tissue antigens. Yet, the expression of the transcripts varied remarkably among the individual thymic samples. In addition, S-Ag, RPE65 and IRBP were detected by immunostaining in rare cells in sections of human thymi by antibodies against these proteins. Quantitative real-time RT-PCR analysis revealed that the retinal antigen transcripts in the human thymus are present at trace levels, that are lower by approximately five orders of magnitude than those in the retina. Our observations thus support the notions that thymic expression is a common feature for all tissue-specific antigens and that the levels of expression play a role in determining the susceptibility to autoimmunity against these molecules.

Keywords: autoimmunity; retinal antigen; susceptibility to disease; tolerance; tumor immunity.
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