Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1984 Apr 1;159(4):1149–1168. doi: 10.1084/jem.159.4.1149

Phenotypic characterization and ontogeny of mesodermal-derived and endocrine epithelial components of the human thymic microenvironment

PMCID: PMC2187287  PMID: 6200562

Abstract

Using murine monoclonal antibodies TE-4 and TE-7 raised against human thymic stroma, we identified two distinct and mutually exclusive thymic microenvironment components: the thymic endocrine epithelium (TE-4+) and mesodermal-derived fibrous stroma (TE-7+). TE-4-reactive epithelium did not react with antibody TE-7, contained thymosin alpha 1 and keratin, and expressed other known markers of thymic endocrine epithelium (A2B5 and p19). Moreover, TE-4+ thymic epithelial cells strongly expressed class I (HLA-A, -B and -C) and class II (Ia-like) major histocompatibility complex (MHC) antigens. In contrast, TE-7+ thymic fibrous stroma did not react with antibody TE-4, did not contain thymosin alpha 1 nor keratin, and did not express the thymic endocrine epithelium markers A2B5 and p19. TE-7+ thymic stromal cells weakly expressed class I and did not express class II MHC antigens. Both TE-4+ and TE-7+ thymic microenvironment compartments were identifiable in thymus from 7 wk gestation through adult life. At 7 wk fetal gestation, TE-7+ stroma surrounded a cylindrical TE-4+, A2B5+ thymic epithelial rudiment. Between 10 and 15 wk fetal gestation, TE-7+ thymic stroma surrounded early thymic lobules. By 15 wk fetal gestation, antibody TE- 4 defined subcapsular cortical and medullary zones of endocrine thymic epithelium, while antibody TE-7 bound to interlobular fibrous septae, vessels, and thymic fibrous capsule. While otherwise specific for endocrine thymic epithelium, antibody TE-4 reacted with the basal layer of squamous epithelium in skin, tonsil, conjunctiva, and upper esophagus.

Full Text

The Full Text of this article is available as a PDF (3.9 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AUERBACH R. Experimental analysis of the origin of cell types in the development of the mouse thymus. Dev Biol. 1961 Jun;3:336–354. doi: 10.1016/0012-1606(61)90051-3. [DOI] [PubMed] [Google Scholar]
  2. AUERBACH R. Morphogenetic interactions in the development of the mouse thymus gland. Dev Biol. 1960 Jun;2:271–284. doi: 10.1016/0012-1606(60)90009-9. [DOI] [PubMed] [Google Scholar]
  3. Beardsley T. R., Pierschbacher M., Wetzel G. D., Hays E. F. Induction of T-cell maturation by a cloned line of thymic epithelium (TEPI). Proc Natl Acad Sci U S A. 1983 Oct;80(19):6005–6009. doi: 10.1073/pnas.80.19.6005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bhan A. K., Reinherz E. L., Poppema S., McCluskey R. T., Schlossman S. F. Location of T cell and major histocompatibility complex antigens in the human thymus. J Exp Med. 1980 Oct 1;152(4):771–782. doi: 10.1084/jem.152.4.771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chu A. C., Patterson J. A., Goldstein G., Berger C. L., Takezaki S., Edelson R. L. Thymopoietin-like substance in human skin. J Invest Dermatol. 1983 Sep;81(3):194–197. doi: 10.1111/1523-1747.ep12517686. [DOI] [PubMed] [Google Scholar]
  6. Cordier A. C., Haumont S. M. Development of thymus, parathyroids, and ultimo-branchial bodies in NMRI and nude mice. Am J Anat. 1980 Mar;157(3):227–263. doi: 10.1002/aja.1001570303. [DOI] [PubMed] [Google Scholar]
  7. Eisenbarth G. S., Shimizu K., Bowring M. A., Wells S. Expression of receptors for tetanus toxin and monoclonal antibody A2B5 by pancreatic islet cells. Proc Natl Acad Sci U S A. 1982 Aug;79(16):5066–5070. doi: 10.1073/pnas.79.16.5066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eisenbarth G. S., Walsh F. S., Nirenberg M. Monoclonal antibody to a plasma membrane antigen of neurons. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4913–4917. doi: 10.1073/pnas.76.10.4913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fink P. J., Bevan M. J. H-2 antigens of the thymus determine lymphocyte specificity. J Exp Med. 1978 Sep 1;148(3):766–775. doi: 10.1084/jem.148.3.766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Goldstein A. L., Low T. L., Thurman G. B., Zatz M. M., Hall N., Chen J., Hu S. K., Naylor P. B., McClure J. E. Current status of thymosin and other hormones of the thymus gland. Recent Prog Horm Res. 1981;37:369–415. doi: 10.1016/b978-0-12-571137-1.50012-8. [DOI] [PubMed] [Google Scholar]
  11. Haynes B. F., Eisenbarth G. S., Fauci A. S. Human lymphocyte antigens: production of a monoclonal antibody that defines functional thymus-derived lymphocyte subsets. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5829–5833. doi: 10.1073/pnas.76.11.5829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Haynes B. F., Hensley L. L., Jegasothy B. V. Differentiation of human T lymphocytes: II. Phenotypic difference in skin and blood malignant T-cells in cutaneous T-cell lymphoma. J Invest Dermatol. 1982 Apr;78(4):323–326. doi: 10.1111/1523-1747.ep12507406. [DOI] [PubMed] [Google Scholar]
  13. Haynes B. F., Mann D. L., Hemler M. E., Schroer J. A., Shelhamer J. H., Eisenbarth G. S., Strominger J. L., Thomas C. A., Mostowski H. S., Fauci A. S. Characterization of a monoclonal antibody that defines an immunoregulatory T cell subset for immunoglobulin synthesis in humans. Proc Natl Acad Sci U S A. 1980 May;77(5):2914–2918. doi: 10.1073/pnas.77.5.2914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Haynes B. F., Reisner E. G., Hemler M. E., Strominger J. L., Eisenbarth G. S. Description of monoclonal antibody defining an HLA allotypic determinant that includes specificities within the B5 cross-reacting group. Hum Immunol. 1982 Jul;4(4):273–285. doi: 10.1016/0198-8859(82)90001-5. [DOI] [PubMed] [Google Scholar]
  15. Haynes B. F., Robert-Guroff M., Metzgar R. S., Franchini G., Kalyanaraman V. S., Palker T. J., Gallo R. C. Monoclonal antibody against human T cell leukemia virus p19 defines a human thymic epithelial antigen acquired during ontogeny. J Exp Med. 1983 Mar 1;157(3):907–920. doi: 10.1084/jem.157.3.907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Haynes B. F., Shimizu K., Eisenbarth G. S. Identification of human and rodent thymic epithelium using tetanus toxin and monoclonal antibody A2B5. J Clin Invest. 1983 Jan;71(1):9–14. doi: 10.1172/JCI110755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Haynes B. F., Warren R. W., Buckley R. H., McClure J. E., Goldstein A. L., Henderson F. W., Hensley L. L., Eisenbarth G. S. Demonstration of abnormalities in expression of thymic epithelial surface antigens in severe cellular immunodeficiency diseases. J Immunol. 1983 Mar;130(3):1182–1188. [PubMed] [Google Scholar]
  18. Janossy G., Thomas J. A., Bollum F. J., Granger S., Pizzolo G., Bradstock K. F., Wong L., McMichael A., Ganeshaguru K., Hoffbrand A. V. The human thymic microenvironment: an immunohistologic study. J Immunol. 1980 Jul;125(1):202–212. [PubMed] [Google Scholar]
  19. Jenkinson E. J., Van Ewijk W., Owen J. J. Major histocompatibility complex antigen expression on the epithelium of the developing thymus in normal and nude mice. J Exp Med. 1981 Feb 1;153(2):280–292. doi: 10.1084/jem.153.2.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kato K., Ikeyama S., Takaoki M., Shino A., Takeuchi M., Kakinuma A. Epithelial cell components immunoreact with anti-serum thymic factor (FTS) antibodies: possible association with intermediate-sized filaments. Cell. 1981 Jun;24(3):885–895. doi: 10.1016/0092-8674(81)90114-8. [DOI] [PubMed] [Google Scholar]
  21. Kruisbeek A. M., Fultz M. J., Sharrow S. O., Singer A., Mond J. J. Early development of the T cell repertoire. In vivo treatment of neonatal mice with anti-Ia antibodies interferes with differentiation of I-restricted T cells but not K/D-restricted T cells. J Exp Med. 1983 Jun 1;157(6):1932–1946. doi: 10.1084/jem.157.6.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kruisbeek A. M., Sharrow S. O., Mathieson B. J., Singer A. The H-2 phenotype of the thymus dictates the self-specificity expressed by thymic but not splenic cytotoxic T lymphocyte precursors in thymus-engrafted nude mice. J Immunol. 1981 Nov;127(5):2168–2176. [PubMed] [Google Scholar]
  23. Lampson L. A., Levy R. Two populations of Ia-like molecules on a human B cell line. J Immunol. 1980 Jul;125(1):293–299. [PubMed] [Google Scholar]
  24. Le Douarin N. M., Jotereau F. V. Tracing of cells of the avian thymus through embryonic life in interspecific chimeras. J Exp Med. 1975 Jul 1;142(1):17–40. doi: 10.1084/jem.142.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Oosterom R., Kater L., Rademakers L. H. How unique is the thymus? Conditioned media from thymus and tonsil epithelial cultures share biological activities in T-cell maturation. Clin Immunol Immunopathol. 1981 Jun;19(3):428–436. doi: 10.1016/0090-1229(81)90085-4. [DOI] [PubMed] [Google Scholar]
  26. Papiernik M. Correlation of lymphocyte transformation and morphology in the human fetal thymus. Blood. 1970 Oct;36(4):470–479. [PubMed] [Google Scholar]
  27. Pereira G., Clermont Y. Distribution of cell web-containing epithelial reticular cells in the rat thymus. Anat Rec. 1971 Apr;169(4):613–626. doi: 10.1002/ar.1091690402. [DOI] [PubMed] [Google Scholar]
  28. Robert-Guroff M., Ruscetti F. W., Posner L. E., Poiesz B. J., Gallo R. C. Detection of the human T cell lymphoma virus p19 in cells of some patients with cutaneous T cell lymphoma and leukemia using a monoclonal antibody. J Exp Med. 1981 Dec 1;154(6):1957–1964. doi: 10.1084/jem.154.6.1957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rouse R. V., Weissman I. L. Microanatomy of the thymus: its relationship to T cell differentiation. Ciba Found Symp. 1981;84:161–177. doi: 10.1002/9780470720660.ch9. [DOI] [PubMed] [Google Scholar]
  30. Rubenfeld M. R., Silverstone A. E., Knowles D. M., Halper J. P., De Sostoa A., Fenoglio C. M., Edelson R. L. Induction of lymphocyte differentiation by epidermal cultures. J Invest Dermatol. 1981 Aug;77(2):221–224. doi: 10.1111/1523-1747.ep12480029. [DOI] [PubMed] [Google Scholar]
  31. Schmitt D., Monier J. C., Dardenne M., Pleau J. M., Deschaux P., Bach J. F. Cytoplasmic localization of FTS (facteur thymique sérique) in thymic epithelial cells. An immunoelectronmicroscopical study. Thymus. 1980 Dec;2(3):177–186. [PubMed] [Google Scholar]
  32. Singer A., Hathcock K. S., Hodes R. J. Self recognition in allogeneic thymic chimeras. Self recognition by T helper cells from thymus-engrafted nude mice is restricted to the thymic H-2 haplotype. J Exp Med. 1982 Jan 1;155(1):339–344. doi: 10.1084/jem.155.1.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Woodcock-Mitchell J., Eichner R., Nelson W. G., Sun T. T. Immunolocalization of keratin polypeptides in human epidermis using monoclonal antibodies. J Cell Biol. 1982 Nov;95(2 Pt 1):580–588. doi: 10.1083/jcb.95.2.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES