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

Hiroshi Takase, Cheng Rong Yu, Rashid M. Mahdi, Daniel C. Douek, Gregory B. DiRusso, Frank M. Midgley, Rajpreet Dogra, Gloria Allende, Eliot Rosenkranz, Alberto Pugliese, Charles E. Egwuagu, Igal Gery

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1131-1140
Number of pages10
JournalInternational Immunology
Volume17
Issue number8
DOIs
StatePublished - Aug 1 2005

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Antigens
Thymus Gland
Retinol-Binding Proteins
Reverse Transcription
gp100 Melanoma Antigen
Recoverin
MART-1 Antigen
Physiological Phenomena
Arrestin
Polymerase Chain Reaction
Eye Diseases
Melanocytes
Autoantigens
Autoimmunity
Immunotherapy
Autoimmune Diseases
Retina
Melanoma
T-Lymphocytes
Messenger RNA

Keywords

  • Autoimmunity
  • Retinal antigen
  • Susceptibility to disease
  • Tolerance
  • Tumor immunity

ASJC Scopus subject areas

  • Immunology

Cite this

Takase, H., Yu, C. R., Mahdi, R. M., Douek, D. C., DiRusso, G. B., Midgley, F. M., ... Gery, I. (2005). Thymic expression of peripheral tissue antigens in humans: A remarkable variability among individuals. International Immunology, 17(8), 1131-1140. https://doi.org/10.1093/intimm/dxh275

Thymic expression of peripheral tissue antigens in humans : A remarkable variability among individuals. / Takase, Hiroshi; Yu, Cheng Rong; Mahdi, Rashid M.; Douek, Daniel C.; DiRusso, Gregory B.; Midgley, Frank M.; Dogra, Rajpreet; Allende, Gloria; Rosenkranz, Eliot; Pugliese, Alberto; Egwuagu, Charles E.; Gery, Igal.

In: International Immunology, Vol. 17, No. 8, 01.08.2005, p. 1131-1140.

Research output: Contribution to journalArticle

Takase, H, Yu, CR, Mahdi, RM, Douek, DC, DiRusso, GB, Midgley, FM, Dogra, R, Allende, G, Rosenkranz, E, Pugliese, A, Egwuagu, CE & Gery, I 2005, 'Thymic expression of peripheral tissue antigens in humans: A remarkable variability among individuals', International Immunology, vol. 17, no. 8, pp. 1131-1140. https://doi.org/10.1093/intimm/dxh275
Takase, Hiroshi ; Yu, Cheng Rong ; Mahdi, Rashid M. ; Douek, Daniel C. ; DiRusso, Gregory B. ; Midgley, Frank M. ; Dogra, Rajpreet ; Allende, Gloria ; Rosenkranz, Eliot ; Pugliese, Alberto ; Egwuagu, Charles E. ; Gery, Igal. / Thymic expression of peripheral tissue antigens in humans : A remarkable variability among individuals. In: International Immunology. 2005 ; Vol. 17, No. 8. pp. 1131-1140.
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