Autoimmune thyroid disease occurs in some complete DiGeorge anomaly patients after thymus transplantation. This study was designed to assess the effect of culture of thymus tissue on the expression of genes involved in the development of autoimmunity. The expression of autoimmune regulator (AIRE), thyroglobulin (TG), thyroid peroxidase (TPO), and cytokeratin RNAs was examined in thymocytes and thymus tissue on the day of thymus harvest and after 14 and 21 days of culture. Immunohistochemistry was used to evaluate the cytokeratin expression in the thymus tissue. AIRE, TG, TPO, and cytokeratin mRNAs were found in harvest-day, 14-day and 21-day cultured tissues. Levels of AIRE, TG, and cytokeratin mRNAs were mostly higher after culture compared to expression on the harvest day, likely secondary to thymocyte depletion.
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This work was supported by the National Institutes of Health (grants R01-AI47040, R01-AI 54843), and FDA (grant FD-R-002606). The statistical support was provided by the Biostatistics Core of Duke Translational Medicine Institute, funded by the Grant Number 1 UL1 RR024128-01 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research.
Haynes BF, Markert ML, Sempowski GD, Patel DD, Hale LP. The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection. Annu Rev Immunol. 2000;18:529–60.PubMedCrossRefGoogle Scholar
Markert ML, Boeck A, Hale LP, Kloster AL, McLaughlin TM, Batchvarova MN, et al. Transplantation of thymus tissue in complete DiGeorge syndrome. N Engl J Med. 1999;341(16):1180–9.PubMedCrossRefGoogle Scholar
Markert ML, Sarzotti M, Ozaki DA, Sempowski GD, Rhein ME, Hale LP, et al. Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients. Blood. 2003;102(3):1121–30.PubMedCrossRefGoogle Scholar
Markert ML, Devlin BH, Alexieff MJ, Li J, McCarthy EA, Gupton SE, et al. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood. 2007;109(10):4539–47.PubMedCrossRefGoogle Scholar
Kyewski B, Derbinski J, Gotter J, Klein L. Promiscuous gene expression and central T-cell tolerance: more than meets the eye. Trends Immunol. 2002;23(7):364–71.PubMedCrossRefGoogle Scholar
Derbinski J, Schulte A, Kyewski B, Klein L. Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nat Immunol. 2001;2(11):1032–9.PubMedCrossRefGoogle Scholar
Derbinski J, Gabler J, Brors B, Tierling S, Jonnakuty S, Hergenhahn M, et al. Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels. J Exp Med. 2005;202(1):33–45.PubMedCrossRefGoogle Scholar
Klein L, Kyewski B. “Promiscuous” expression of tissue antigens in the thymus: a key to T-cell tolerance and autoimmunity? J Mol Med. 2000;78(9):483–94.PubMedCrossRefGoogle Scholar
Magalhaes DA, Silveira EL, Junta CM, Sandrin-Garcia P, Fachin AL, Donadi EA, et al. Promiscuous gene expression in the thymus: the root of central tolerance. Clin Dev Immunol. 2006;13(2–4):81–99.PubMedCrossRefGoogle Scholar
Spitzweg C, Joba W, Heufelder AE. Expression of thyroid-related genes in human thymus. Thyroid. 1999;9(2):133–41.PubMedCrossRefGoogle Scholar
Scuccimarri R, Rodd C. Thyroid abnormalities as a feature of DiGeorge syndrome: a patient report and review of the literature. J Pediatr Endocrinol Metab. 1998;11(2):273–6.PubMedGoogle Scholar
Ai J, Leonhardt JM, Heymann WR. Autoimmune thyroid diseases: etiology, pathogenesis, and dermatologic manifestations. J Am Acad Dermatol. 2003;48(5):641–59. quiz 660–662.PubMedCrossRefGoogle Scholar
Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins SP, Turley SJ, et al. Projection of an immunological self shadow within the thymus by the aire protein. Science. 2002;298(5597):1395–401. (New York, NY).PubMedCrossRefGoogle Scholar
Wara DW, Golbus MS, Ammann AJ. Fetal thymus glands obtained from prostaglandin-induced abortions. Cellular immune function in vitro and evidence of in vivo thymocyte activity following transplantation. Transplantation. 1974;18(5):387–90.PubMedCrossRefGoogle Scholar
Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29(9):e45.PubMedCrossRefGoogle Scholar
Markert ML, Alexieff MJ, Li J, Sarzotti M, Ozaki DA, Devlin BH, et al. Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome. Blood. 2004;104(8):2574–81.PubMedCrossRefGoogle Scholar
Chin RK, Lo JC, Kim O, Blink SE, Christiansen PA, Peterson P, et al. Lymphotoxin pathway directs thymic Aire expression. Nat Immunol. 2003;4(11):1121–7.PubMedCrossRefGoogle Scholar
Farr AG, Dooley JL, Erickson M. Organization of thymic medullary epithelial heterogeneity: implications for mechanisms of epithelial differentiation. Immunol Rev. 2002;189:20–7.PubMedCrossRefGoogle Scholar
Gotter J, Brors B, Hergenhahn M, Kyewski B. Medullary epithelial cells of the human thymus express a highly diverse selection of tissue-specific genes colocalized in chromosomal clusters. J Exp Med. 2004;199(2):155–66.PubMedCrossRefGoogle Scholar