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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Apr 1;89(7):2526–2530. doi: 10.1073/pnas.89.7.2526

Tolerance induction by thymic medullary epithelium.

M W Hoffmann 1, J Allison 1, J F Miller 1
PMCID: PMC48694  PMID: 1557355

Abstract

To study the role of thymic medullary epithelium in tolerance induction, the third and fourth branchial clefts of embryos from E mu-Kb transgenic mice, which express the major histocompatibility complex class I antigen H-2Kb exclusively on medullary thymic epithelium, were grafted to athymic nude mice. The grafts differentiated into tissue that morphologically resembled normal thymus. These grafts expressed the H-2Kb antigen appropriately and gave rise to a functional T cell repertoire. In vivo tolerance to H-2Kb disparate skin grafts was invariably found in mice expressing H-2Kb in the medulla or in both medulla and cortex of C57BL/6 branchial cleft-grafted controls. In marked contrast, in vitro cytotoxicity assays demonstrated reactivity toward H-2Kb in the presence of interleukin 2, and limiting-dilution analyses showed similar frequencies of cytolytic T cell precursors reactive to H-2Kb and to third-party stimulators. Medullary epithelium can, therefore, induce split tolerance, in which in vivo tolerance is accompanied by strong in vitro responses in the presence of interleukin 2.

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Selected References

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  1. Allison J., Müllbacher A., Cox K., Morahan G., Boyd R., Scollay R., Blanden R. V., Miller J. F. Selection of the T-cell repertoire in transgenic mice expressing a transplantation antigen in distinct thymus subsets. Proc Biol Sci. 1990 Sep 22;241(1302):170–178. doi: 10.1098/rspb.1990.0082. [DOI] [PubMed] [Google Scholar]
  2. Dialynas D. P., Quan Z. S., Wall K. A., Pierres A., Quintáns J., Loken M. R., Pierres M., Fitch F. W. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol. 1983 Nov;131(5):2445–2451. [PubMed] [Google Scholar]
  3. Gao E. K., Lo D., Sprent J. Strong T cell tolerance in parent----F1 bone marrow chimeras prepared with supralethal irradiation. Evidence for clonal deletion and anergy. J Exp Med. 1990 Apr 1;171(4):1101–1121. doi: 10.1084/jem.171.4.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Good M. F., Pyke K. W., Nossal G. J. Functional clonal deletion of cytotoxic T-lymphocyte precursors in chimeric thymus produced in vitro from embryonic Anlagen. Proc Natl Acad Sci U S A. 1983 May;80(10):3045–3049. doi: 10.1073/pnas.80.10.3045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hämmerling G. J., Schönrich G., Momburg F., Auphan N., Malissen M., Malissen B., Schmitt-Verhulst A. M., Arnold B. Non-deletional mechanisms of peripheral and central tolerance: studies with transgenic mice with tissue-specific expression of a foreign MHC class I antigen. Immunol Rev. 1991 Aug;122:47–67. doi: 10.1111/j.1600-065x.1991.tb00596.x. [DOI] [PubMed] [Google Scholar]
  6. Jordan R. K., Robinson J. H., Hopkinson N. A., House K. C., Bentley A. L. Thymic epithelium and the induction of transplantation tolerance in nude mice. Nature. 1985 Apr 4;314(6010):454–456. doi: 10.1038/314454a0. [DOI] [PubMed] [Google Scholar]
  7. Khazaal I., Salaün J., Coltey M., Calman F., Le Douarin N. Restoration of T-cell function in nude mice by grafting the epitheliomesenchymal thymic rudiment from 10-day-old euthymic embryos. Cell Differ Dev. 1989 May;26(3):211–220. doi: 10.1016/0922-3371(89)90752-1. [DOI] [PubMed] [Google Scholar]
  8. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  9. Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
  10. Ozato K., Sachs D. H. Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2b haplotype reveal genetic control of isotype expression. J Immunol. 1981 Jan;126(1):317–321. [PubMed] [Google Scholar]
  11. Ramsdell F., Lantz T., Fowlkes B. J. A nondeletional mechanism of thymic self tolerance. Science. 1989 Nov 24;246(4933):1038–1041. doi: 10.1126/science.2511629. [DOI] [PubMed] [Google Scholar]
  12. Roberts J. L., Sharrow S. O., Singer A. Clonal deletion and clonal anergy in the thymus induced by cellular elements with different radiation sensitivities. J Exp Med. 1990 Mar 1;171(3):935–940. doi: 10.1084/jem.171.3.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Salaün J., Bandeira A., Khazaal I., Calman F., Coltey M., Coutinho A., Le Douarin N. M. Thymic epithelium tolerizes for histocompatibility antigens. Science. 1990 Mar 23;247(4949 Pt 1):1471–1474. doi: 10.1126/science.247.4949.1471. [DOI] [PubMed] [Google Scholar]
  14. Sprent J., Webb S. R. Function and specificity of T cell subsets in the mouse. Adv Immunol. 1987;41:39–133. doi: 10.1016/s0065-2776(08)60030-9. [DOI] [PubMed] [Google Scholar]
  15. Von Boehmer H., Schubiger K. Thymocytes appear to ignore class I major histocompatibility complex antigens expressed on thymus epithelial cells. Eur J Immunol. 1984 Nov;14(11):1048–1052. doi: 10.1002/eji.1830141116. [DOI] [PubMed] [Google Scholar]
  16. Webb S. R., Sprent J. Tolerogenicity of thymic epithelium. Eur J Immunol. 1990 Nov;20(11):2525–2528. doi: 10.1002/eji.1830201127. [DOI] [PubMed] [Google Scholar]
  17. von Boehmer H. Developmental biology of T cells in T cell-receptor transgenic mice. Annu Rev Immunol. 1990;8:531–556. doi: 10.1146/annurev.iy.08.040190.002531. [DOI] [PubMed] [Google Scholar]
  18. von Boehmer H., Hafen K. Minor but not major histocompatibility antigens of thymus epithelium tolerize precursors of cytolytic T cells. Nature. 1986 Apr 17;320(6063):626–628. doi: 10.1038/320626a0. [DOI] [PubMed] [Google Scholar]

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