Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1987 Jun;127(3):580–591.

Adrenocortical cells of the zona reticularis normally express HLA-DR antigenic determinants.

E L Khoury, J S Greenspan, F S Greenspan
PMCID: PMC1899772  PMID: 2438943

Abstract

A distinct population of normal human adrenocortical cells from adult glands spontaneously express HLA-DR, and occasionally also HLA-DQ, antigenic determinants in vivo and in vitro, as detected by immunofluorescence techniques using monoclonal antibodies on frozen tissue sections, primary cultures, and viable cell suspensions. In vivo, these antigenic determinants were found to be confined to the compact-type cells in the zona reticularis. In vitro, the adrenocortical identity of these HLA-DR+ cells was conclusively established by the characteristic change in their morphologic features induced by ACTH1-24 and by the simultaneous detection of tissue-specific adrenal autoantigens in double-label immunofluorescence staining. The cell surface expression of HLA-DR determinants by compact cells persisted in culture for several weeks and was not significantly affected by treatment with ACTH1-24. On the other hand, fetal adrenocortical cells of both transient and definitive zones were invariably negative for the expression of these HLA Class II antigenic determinants. Because normal human adrenocortical cells also express on their surface the molecules which constitute specific autoantigens in autoimmune adrenalitis, these findings argue against the notion that an ectopic HLA-DR expression associated with an otherwise "silent" autoantigen might trigger an organ-specific autoimmune response against endocrine cells. In addition, the expression of HLA-DR determinants by viable normal reticularis cells provides a readily detectable surface marker which may allow the physical separation of this population for studies in vitro.

Full text

PDF
580

Images in this article

584Figure 1
on p.584
584Figure 2
on p.584
586Figure 3
on p.586
586Figure 4
on p.586
587Figure 5
on p.587

Selected References

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

  1. Abo T., Balch C. M. A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol. 1981 Sep;127(3):1024–1029. [PubMed] [Google Scholar]
  2. Benacerraf B. Significance and biological function of class II MHC molecules. Rous-Whipple Award lecture 1985. Am J Pathol. 1985 Sep;120(3):334–343. [PMC free article] [PubMed] [Google Scholar]
  3. Bottazzo G. F., Pujol-Borrell R., Hanafusa T., Feldmann M. Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity. Lancet. 1983 Nov 12;2(8359):1115–1119. doi: 10.1016/s0140-6736(83)90629-3. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. CARR I. The human adrenal cortex at the time of death. J Pathol Bacteriol. 1959 Oct;78:533–541. doi: 10.1002/path.1700780220. [DOI] [PubMed] [Google Scholar]
  6. Cameron E. H., Jones T., Jones D., Anderson A. B., Griffiths K. Further studies on the relationship between C19- and C21-steroid synthesis in the human adrenal gland. J Endocrinol. 1969 Oct;45(2):215–230. doi: 10.1677/joe.0.0450215. [DOI] [PubMed] [Google Scholar]
  7. Dhom G. The prepuberal and puberal growth of the adrenal (adrenarche). Beitr Pathol. 1973 Dec;150(4):357–377. doi: 10.1016/s0005-8165(73)80086-1. [DOI] [PubMed] [Google Scholar]
  8. Forsum U., Klareskog L., Peterson P. A. Distribution of Ia-antigen-like molecules on non-lymphoid tissues. Scand J Immunol. 1979;9(4):343–349. doi: 10.1111/j.1365-3083.1979.tb03172.x. [DOI] [PubMed] [Google Scholar]
  9. GRANT J. K., SYMINGTON T., DUGUID W. P. Effect of adrenocorticotropic therapy on the in vitro 11beta-hydroxylation of deoxycorticosterone by human adrenal homogenates. J Clin Endocrinol Metab. 1957 Aug;17(8):933–944. doi: 10.1210/jcem-17-8-933. [DOI] [PubMed] [Google Scholar]
  10. GRIFFITHS K., GRANT J. K., SYMINGTON T. A BIOCHEMICAL INVESTIGATION OF THE FUNCTIONAL ZONATION OF THE ADRENAL CORTEX IN MAN. J Clin Endocrinol Metab. 1963 Aug;23:776–785. doi: 10.1210/jcem-23-8-776. [DOI] [PubMed] [Google Scholar]
  11. Guy K., Steel C. M. Interpretation of the specificities of monoclonal antibodies recognising human MHC class II antigens. Clin Exp Immunol. 1985 Jan;59(1):251–254. [PMC free article] [PubMed] [Google Scholar]
  12. Hanafusa T., Pujol-Borrell R., Chiovato L., Russell R. C., Doniach D., Bottazzo G. F. Aberrant expression of HLA-DR antigen on thyrocytes in Graves' disease: relevance for autoimmunity. Lancet. 1983 Nov 12;2(8359):1111–1115. doi: 10.1016/s0140-6736(83)90628-1. [DOI] [PubMed] [Google Scholar]
  13. Hart D. N., Fabre J. W. Endogenously produced Ia antigens within cells of convoluted tubules of rat kidney. J Immunol. 1981 Jun;126(6):2109–2113. [PubMed] [Google Scholar]
  14. Kennerson A. R., McDonald D. A., Adams J. B. Dehydroepiandrosterone sulfotransferase localization in human adrenal glands: a light and electron microscopic study. J Clin Endocrinol Metab. 1983 Apr;56(4):786–790. doi: 10.1210/jcem-56-4-786. [DOI] [PubMed] [Google Scholar]
  15. Khoury E. L., Hammond L., Bottazzo G. F., Doniach D. Surface-reactive antibodies to human adrenal cells in Addison's disease. Clin Exp Immunol. 1981 Jul;45(1):48–55. [PMC free article] [PubMed] [Google Scholar]
  16. Khoury E. L. Reexpression of blood group ABH antigens on the surface of human thyroid cells in culture. J Cell Biol. 1982 Jul;94(1):193–200. doi: 10.1083/jcb.94.1.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Klareskog L., Forsum U., Peterson P. A. Hormonal regulation of the expression of Ia antigens on mammary gland epithelium. Eur J Immunol. 1980 Dec;10(12):958–963. doi: 10.1002/eji.1830101212. [DOI] [PubMed] [Google Scholar]
  18. Ko H. S., Fu S. M., Winchester R. J., Yu D. T., Kunkel H. G. Ia determinants on stimulated human T lymphocytes. Occurrence on mitogen- and antigen-activated T cells. J Exp Med. 1979 Aug 1;150(2):246–255. doi: 10.1084/jem.150.2.246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Koyama K., Fukunishi T., Barcos M., Tanigaki N., Pressman D. Human Ia-like antigens in non-lymphoid organs. Immunology. 1979 Oct;38(2):333–341. [PMC free article] [PubMed] [Google Scholar]
  20. Lipinski M., Braham K., Caillaud J. M., Carlu C., Tursz T. HNK-1 antibody detects an antigen expressed on neuroectodermal cells. J Exp Med. 1983 Nov 1;158(5):1775–1780. doi: 10.1084/jem.158.5.1775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lloyd R. V., Johnson T. L., Blaivas M., Sisson J. C., Wilson B. S. Detection of HLA-DR antigens in paraffin-embedded thyroid epithelial cells with a monoclonal antibody. Am J Pathol. 1985 Jul;120(1):106–111. [PMC free article] [PubMed] [Google Scholar]
  22. Lowry R., Goguen J., Carpenter C. B., Strom T. B., Garovoy M. R. Improved B cell typing for HLA-DR using nylon wool column enriched B lymphocyte preparations. Tissue Antigens. 1979 Oct;14(4):325–330. doi: 10.1111/j.1399-0039.1979.tb00856.x. [DOI] [PubMed] [Google Scholar]
  23. Lu C. Y., Changelian P. S., Unanue E. R. Alpha-fetoprotein inhibits macrophage expression of Ia antigens. J Immunol. 1984 Apr;132(4):1722–1727. [PubMed] [Google Scholar]
  24. McDevitt H. O. The HLA system and its relation to disease. Hosp Pract (Off Ed) 1985 Jul 15;20(7):57–72. doi: 10.1080/21548331.1985.11703093. [DOI] [PubMed] [Google Scholar]
  25. McDevitt H. O. The molecular basis of autoimmunity. Clin Res. 1986 Apr;34(2):163–175. [PubMed] [Google Scholar]
  26. Natali P. G., De Martino C., Quaranta V., Nicotra M. R., Frezza F., Pellegrino M. A., Ferrone S. Expression of Ia-like antigens in normal human nonlymphoid tissues. Transplantation. 1981 Jan;31(1):75–78. doi: 10.1097/00007890-198101000-00017. [DOI] [PubMed] [Google Scholar]
  27. Natali P. G., Quaranta V., Nicotra M. R., Apollonj C., Pellegrino M. A., Ferrone S. Tissue distribution of Ia-like antigens in different species: analysis with monoclonal antibodies. Transplant Proc. 1981 Mar;13(1 Pt 2):1026–1029. [PubMed] [Google Scholar]
  28. Orentreich N., Brind J. L., Rizer R. L., Vogelman J. H. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab. 1984 Sep;59(3):551–555. doi: 10.1210/jcem-59-3-551. [DOI] [PubMed] [Google Scholar]
  29. Parker L. N., Odell W. D. Control of adrenal androgen secretion. Endocr Rev. 1980 Fall;1(4):392–410. doi: 10.1210/edrv-1-4-392. [DOI] [PubMed] [Google Scholar]
  30. Parker L. N., Odell W. D. Evidence for existence of cortical androgen-stimulating hormone. Am J Physiol. 1979 Jun;236(6):E616–E620. doi: 10.1152/ajpendo.1979.236.6.E616. [DOI] [PubMed] [Google Scholar]
  31. Ramachandran J., Suyama A. T. Inhibition of replication of normal adrenocortical cells in culture by adrenocorticotropin. Proc Natl Acad Sci U S A. 1975 Jan;72(1):113–117. doi: 10.1073/pnas.72.1.113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. A monoclonal antibody reactive with the human cytotoxic/suppressor T cell subset previously defined by a heteroantiserum termed TH2. J Immunol. 1980 Mar;124(3):1301–1307. [PubMed] [Google Scholar]
  33. Reinherz E. L., Kung P. C., Pesando J. M., Ritz J., Goldstein G., Schlossman S. F. Ia determinants on human T-cell subsets defined by monoclonal antibody. Activation stimuli required for expression. J Exp Med. 1979 Dec 1;150(6):1472–1482. doi: 10.1084/jem.150.6.1472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sarkar S., Glassy M. C., Ferrone S., Jones O. W. Cell cycle and the differential expression of HLA-A,B and HLA-DR antigens on human B lymphoid cells. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7297–7301. doi: 10.1073/pnas.77.12.7297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Schuller-Petrovic S., Gebhart W., Lassmann H., Rumpold H., Kraft D. A shared antigenic determinant between natural killer cells and nervous tissue. Nature. 1983 Nov 10;306(5939):179–181. doi: 10.1038/306179a0. [DOI] [PubMed] [Google Scholar]
  36. Scott H., Solheim B. G., Brandtzaeg P., Thorsby E. HLA-DR-like antigens in the epithelium of the human small intestine. Scand J Immunol. 1980;12(1):77–82. doi: 10.1111/j.1365-3083.1980.tb00043.x. [DOI] [PubMed] [Google Scholar]
  37. Simonian M. H., Gill G. N. Regulation of the fetal human adrenal cortex: effects of adrenocorticotropin on growth and function of monolayer cultures of fetal and definitive zone cells. Endocrinology. 1981 May;108(5):1769–1779. doi: 10.1210/endo-108-5-1769. [DOI] [PubMed] [Google Scholar]
  38. Stein H., Lennert K., Feller A. C., Mason D. Y. Immunohistological analysis of human lymphoma: correlation of histological and immunological categories. Adv Cancer Res. 1984;42:67–147. doi: 10.1016/s0065-230x(08)60456-x. [DOI] [PubMed] [Google Scholar]
  39. Wagner D. D., Olmsted J. B., Marder V. J. Immunolocalization of von Willebrand protein in Weibel-Palade bodies of human endothelial cells. J Cell Biol. 1982 Oct;95(1):355–360. doi: 10.1083/jcb.95.1.355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wiman K., Curman B., Forsum U., Klareskog L., Malmnäs-Tjernlund U., Rask L., Trägårdh L., Peterson P. A. Occurrence of Ia antigens on tissues on non-lymphoid origin. Nature. 1978 Dec 14;276(5689):711–713. doi: 10.1038/276711a0. [DOI] [PubMed] [Google Scholar]
  41. Winchester R. J., Ross G. D., Jarowski C. I., Wang C. Y., Halper J., Broxmeyer H. E. Expression of Ia-like antigen molecules on human granulocytes during early phases of differentiation. Proc Natl Acad Sci U S A. 1977 Sep;74(9):4012–4016. doi: 10.1073/pnas.74.9.4012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Yamaji T., Ibayashi H. Plasma dehydroepiandrosterone sulfate in normal and pathological conditions. J Clin Endocrinol Metab. 1969 Feb;29(2):273–278. doi: 10.1210/jcem-29-2-273. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES