Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1985 Sep;76(3):1140–1146. doi: 10.1172/JCI112069

Thymoma epithelial cells secrete thymic hormone but do not express class II antigens of the major histocompatibility complex.

W Savino, G Manganella, J M Verley, A Wolff, S Berrih, P Levasseur, J P Binet, M Dardenne, J F Bach
PMCID: PMC424007  PMID: 2413072

Abstract

17 thymomas were studied by indirect immunofluorescence for the presence of thymic hormones and antigens of the major histocompatibility complex (MHC). The thymoma epithelial cells (specifically identified by their keratin content) contained thymic hormones (thymulin and thymosin alpha 1), a finding corroborated by the observation of elevated thymulin serum levels. In contrast with normal or hyperplastic thymuses, thymoma epithelial cells did not express HLA-DR and HLA-DC antigens as assessed by immunofluorescence as well as immunoblot analyses. Conversely, MHC class I antigens (HLA-ABC) were normally expressed. Thus, we conclude that thymoma epithelial cells are endocrinologically active but are defective for the expression of some MHC products (class II molecules) known to play an essential role in intrathymic T cell differentiation.

Full text

PDF
1140

Images in this article

Selected References

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

  1. Auger C., Monier J. C., Dardenne M., Pleau J. M., Bach J. F. Identification of FTS (facteur thymique serique) on thymus ultrathin sections using monoclonal antibodies. Immunol Lett. 1982 Oct;5(4):213–216. doi: 10.1016/0165-2478(82)90137-7. [DOI] [PubMed] [Google Scholar]
  2. Bach J. F., Papiernik M., Levasseur P., Dardenne M., Barois A., Le Brigand H. Evidence for a serum-factor secreted by the human thymus. Lancet. 1972 Nov 18;2(7786):1056–1058. doi: 10.1016/s0140-6736(72)92339-2. [DOI] [PubMed] [Google Scholar]
  3. Bach J. F. Thymic hormones. J Immunopharmacol. 1979;1(3):277–310. doi: 10.3109/08923977909026377. [DOI] [PubMed] [Google Scholar]
  4. Battifora H., Sun T. T., Bahu R. M., Rao S. The use of antikeratin antiserum as a diagnostic tool: thymoma versus lymphoma. Hum Pathol. 1980 Nov;11(6):635–641. doi: 10.1016/s0046-8177(80)80074-8. [DOI] [PubMed] [Google Scholar]
  5. Berrih S., Savino W., Azoulay M., Dardenne M., Bach J. F. Production of anti-thymulin (FTS) monoclonal antibodies by immunization against human thymic epithelial cells. J Histochem Cytochem. 1984 Apr;32(4):432–438. doi: 10.1177/32.4.6200531. [DOI] [PubMed] [Google Scholar]
  6. Brodsky F. M. A matrix approach to human class II histocompatibility antigens: reactions of four monoclonal antibodies with the products of nine haplotypes. Immunogenetics. 1984;19(3):179–194. doi: 10.1007/BF00364762. [DOI] [PubMed] [Google Scholar]
  7. Chen Y. X., Evans R. L., Pollack M. S., Lanier L. L., Phillips J. H., Rousso C., Warner N. L., Brodsky F. M. Characterization and expression of the HLA-DC antigens defined by anti-Leu 10. Hum Immunol. 1984 Aug;10(4):221–235. doi: 10.1016/0198-8859(84)90088-0. [DOI] [PubMed] [Google Scholar]
  8. Chollet P., Plagne R., Fonck Y., Chassagne J., Bétail G., Dardenne M., Bach J. F. Thymoma with hypersecretion of thymic hormone. Thymus. 1981 Dec;3(6):321–334. [PubMed] [Google Scholar]
  9. Cohen S., Berrih S., Dardenne M., Bach J. F. Régulation in vitro de la sécrétion de thymuline (FTS) par les cellules épithéliales thymiques humaines. C R Seances Acad Sci III. 1983;297(2):63–65. [PubMed] [Google Scholar]
  10. Crevat D., Kalil J., Rosa F., Fellous M. Présence de deux épitopes différents sur la beta 2-microglobuline humaine définis par des anticorps monoclonaux. Ann Immunol (Paris) 1983 Jan-Feb;134C(1):31–41. [PubMed] [Google Scholar]
  11. Dalakas M. C., Engel W. K., McClure J. E., Goldstein A. L., Askanas V. Immunocytochemical localization of thymosin-alpha 1 in thymic epithelial cells of normal and myasthenia gravis patients and in thymic cultures. J Neurol Sci. 1981 May;50(2):239–247. doi: 10.1016/0022-510x(81)90170-2. [DOI] [PubMed] [Google Scholar]
  12. Franceschi C., Licastro F., Chiricolo M., Bonetti F., Zannotti M., Fabris N., Mocchegiani E., Fantini M. P., Paolucci P., Masi M. Deficiency of autologous mixed lymphocyte reactions and serum thymic factor level in Down's syndrome. J Immunol. 1981 Jun;126(6):2161–2164. [PubMed] [Google Scholar]
  13. Garaci E., Ronchetti R., Del Gobbo V., Tramutoli G., Rinaldi-Garaci C., Imperato C. Decreased serum thymic factor activity in asthmatic children. J Allergy Clin Immunol. 1978 Dec;62(6):357–362. doi: 10.1016/0091-6749(78)90136-7. [DOI] [PubMed] [Google Scholar]
  14. Goldstein A. L., Low T. L., McAdoo M., McClure J., Thurman G. B., Rossio J., Lai C. Y., Chang D., Wang S. S., Harvey C. Thymosin alpha1: isolation and sequence analysis of an immunologically active thymic polypeptide. Proc Natl Acad Sci U S A. 1977 Feb;74(2):725–729. doi: 10.1073/pnas.74.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Goldstein G. The isolation of thymopoietin (thymin). Ann N Y Acad Sci. 1975 Feb 28;249:177–185. doi: 10.1111/j.1749-6632.1975.tb29067.x. [DOI] [PubMed] [Google Scholar]
  16. Haritos A. A., Tsolas O., Horecker B. L. Distribution of prothymosin alpha in rat tissues. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1391–1393. doi: 10.1073/pnas.81.5.1391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Hirokawa K., McClure J. E., Goldstein A. L. Age-related changes in localization of thymosin in the human thymus. Thymus. 1982 Jan;4(1):19–29. [PubMed] [Google Scholar]
  19. Iwata T., Incefy G. S., Good R. A., Cunningham-Rundles S., Dardenne M., Kapoor N., Kirkpatrick D., O'Reilly R. J. Circulating thymic hormone levels in severe combined immunodeficiency. Clin Exp Immunol. 1983 Jul;53(1):1–9. [PMC free article] [PubMed] [Google Scholar]
  20. Jambon B., Montagne P., Bene M. C., Brayer M. P., Faure G., Duheille J. Immunohistologic localization of "facteur thymique serique" (FTS) in human thymic epithelium. J Immunol. 1981 Nov;127(5):2055–2059. [PubMed] [Google Scholar]
  21. 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]
  22. Kirkpatrick C. H., Greenberg L. E., Chapman S. W., Goldstein G., Lewis V. M., Twomey J. J. Plasma thymic hormone activity in patients with chronic mucocutaneous candidiasis. Clin Exp Immunol. 1978 Dec;34(3):311–317. [PMC free article] [PubMed] [Google Scholar]
  23. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Levine G. D., Rosai J. Thymic hyperplasia and neoplasia: a review of current concepts. Hum Pathol. 1978 Sep;9(5):495–515. doi: 10.1016/s0046-8177(78)80131-2. [DOI] [PubMed] [Google Scholar]
  26. Löning T., Caselitz J., Otto H. F. The epithelial framework of the thymus in normal and pathological conditions. Immunohistochemical demonstration of keratin in an autopsy series. Virchows Arch A Pathol Anat Histol. 1981;392(1):7–20. doi: 10.1007/BF00430544. [DOI] [PubMed] [Google Scholar]
  27. McClure J. E., Lameris N., Wara D. W., Goldstein A. L. Immunochemical studies on thymosin: radioimmunoassay of thymosin alpha 1. J Immunol. 1982 Jan;128(1):368–375. [PubMed] [Google Scholar]
  28. Monier J. C., Dardenne M., Pléau J. M., Schmitt D., Deschaux P., Bach J. F. Characterization of facteur thymique sérique (FTS) in the thymus. I. Fixation of anti-FTS antibodies on thymic reticulo-epithelial cells. Clin Exp Immunol. 1980 Dec;42(3):470–476. [PMC free article] [PubMed] [Google Scholar]
  29. Natali P. G., Segatto O., Ferrone S., Tosi R., Corte G. Differential tissue distribution and ontogeny of DC-1 and HLA-DR antigens. Immunogenetics. 1984;19(2):109–116. doi: 10.1007/BF00387853. [DOI] [PubMed] [Google Scholar]
  30. Rebaï N., Malissen B. Structural and genetic analyses of HLA class I molecules using monoclonal xenoantibodies. Tissue Antigens. 1983 Aug;22(2):107–117. doi: 10.1111/j.1399-0039.1983.tb01176.x. [DOI] [PubMed] [Google Scholar]
  31. Rouse R. V., Parham P., Grumet F. C., Weissman I. L. Expression of HLA antigens by human thymic epithelial cells. Hum Immunol. 1982 Aug;5(1):21–34. doi: 10.1016/0198-8859(82)90028-3. [DOI] [PubMed] [Google Scholar]
  32. Rouse R. V., van Ewijk W., Jones P. P., Weissman I. L. Expression of MHC antigens by mouse thymic dendritic cells. J Immunol. 1979 Jun;122(6):2508–2515. [PubMed] [Google Scholar]
  33. Savino W., Dardenne M., Papiernik M., Bach J. F. Thymic hormone-containing cells. Characterization and localization of serum thymic factor in young mouse thymus studied by monoclonal antibodies. J Exp Med. 1982 Aug 1;156(2):628–633. doi: 10.1084/jem.156.2.628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schlesinger D. H., Goldstein G. The amino acid sequence of thymopoietin II. Cell. 1975 Aug;5(4):361–365. doi: 10.1016/0092-8674(75)90054-9. [DOI] [PubMed] [Google Scholar]
  35. Schmitt D., Monier J. C., Dardenne M., Pleau J. M., Bach J. F. Location of FTS (facteur thymique sérique) in the thymus of normal and auto-immune mice. Thymus. 1982 Jul;4(4):221–231. [PubMed] [Google Scholar]
  36. 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]
  37. Sellors T. H., Thackray A. C., Thomson A. D. Tumours of the thymus. A review of 88 operation cases. Thorax. 1967 May;22(3):193–220. doi: 10.1136/thx.22.3.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sun T. T., Bonitz P., Burns W. H. Cell culture of mammalian thymic epithelial cells: growth, structural, and antigenic properties. Cell Immunol. 1984 Jan;83(1):1–13. doi: 10.1016/0008-8749(84)90219-3. [DOI] [PubMed] [Google Scholar]
  39. Twomey J. J., Lewis V. M., Patten B. M., Goldstein G., Good R. A. Myasthenia gravis, thymectomy and serum thymic hormone activity. Am J Med. 1979 Apr;66(4):639–643. doi: 10.1016/0002-9343(79)91175-6. [DOI] [PubMed] [Google Scholar]
  40. Van Ewijk W., Rouse R. V., Weissman I. L. Distribution of H-2 microenvironments in the mouse thymus. Immunoelectron microscopic identification of I-A and H-2K bearing cells. J Histochem Cytochem. 1980 Oct;28(10):1089–1099. doi: 10.1177/28.10.6999083. [DOI] [PubMed] [Google Scholar]
  41. Viac J., Reano A., Brochier J., Staquet M. J., Thivolet J. Reactivity pattern of a monoclonal antikeratin antibody (KL1). J Invest Dermatol. 1983 Oct;81(4):351–354. doi: 10.1111/1523-1747.ep12519941. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES