Skip to main content
SpringerLink
Log in

Immunohistochemical characterization of the thymic microenvironment

A light-microscopic and ultrastructural immunocytochemical study

  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Summary

The epithelial framework of the human thymus has been studied in parallel by immunohistochemical methods at the light- and electron-microscopic levels. Different monoclonal antibodies were used, reacting with components of the major histocompatibility complex, keratins, thymic hormones and other as yet antigenically undefined substances, which show specific immunoreactivities with human thymus epithelial cells.

The electron-microscopic immunocytochemical observations clearly confirm microtopographical differences of epithelial cells not only between the thymic cortex and medulla, but also within the cortex itself. At least four subtypes of epithelial cells could be distinguished: 1) the cortical surface epithelium; 2) the main cortical epithelial cells and thymic nurse cells; 3) the medullary epithelial cells; and 4) the epithelial cells of Hassall's corpuscles.

The various epithelial cell types of the thymus display several common features like tonofilaments, desmosomes and some surface antigens as demonstrated by anti-KiM3. In other respects, however, they differ from each other. The cortical subtype of thymic epithelial cells including the thymic nurse cells shows a distinct pattern of surface antigens reacting positively with antibodies against HLA-DR (anti-HLA-DR) and anti-21A62E. Electron-microscopic immunocytochemistry with these antibodies clearly reveals a surface labeling and a narrow contact to cortical thymocytes particularly in the peripheral cortical regions. An alternative staining pattern is realized by antibodies to some antigens associated with other subtypes of thymic epithelial cells. Medullary epithelial cells as well as the cortical surface epithelium react likewise positively with antibodies to special surface antigens (anti-Ep-1), to special epitopes of cytokeratin (anti-IV/82), and to thymic hormones (anti-FTS). The functional significance of distinct microenvironments within the thymus provided by different epithelial cells is discussed in view of the maturation of T-precursor cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

Anti-X :

anti-X antibody

APUD-cells :

amine precursor uptake and decarboxylation (gastro-intestinal endocrine cells)

DAB :

diamino-benzidine

DMSO :

dimethyl sulfoxide

FTS :

facteur thymique sérique

HLA-A, B, C :

human leucocyte antigen, A, B, C-region related

HLA-DR :

human leucocyte antigen, D-region related

IDC :

interdigitating cell

MHC :

major histocompatibility gene complex

PBS :

phosphate-buffered saline

TNC :

thymic nurse cell

References

  • Auger C, Monier JC, Dardenne M, Pleau JM, Bach JF (1982) Identification of FTS (facteur thymique sérique) on thymus ultrathin sections using monoclonal antibodies. Immunol Lett 5:213–216

    Google Scholar 

  • Bevan MJ (1977) In a radiation chimera host H-2 antigens determine the immune responsiveness of donor cytotoxic cells. Nature 269:417–418

    Google Scholar 

  • Cordier AC, Haumont SA (1980) Development of thymus, parathyroids, and ultimo-branchial bodies in NMRi and nude mice. Am J Anat 157:227–263

    Google Scholar 

  • Dardenne M, Bach JF (1981) Thymic hormones. In: Kendall MD (ed) The thymus gland. Academic Press, London New York, pp 113–131

    Google Scholar 

  • Dardenne M, Papiernik M, Bach JF, Stutman O (1974) Studies on thymus products. 3. Epithelial origin of the serum thymic factor. Immunology 27:299–304

    Google Scholar 

  • Dardenne M, Pleau JM, Man NK, Bach JF (1977) Structural study of a circulating thymic factor: A peptide isolated from pig serum. I. Isolation and purification. J Biol Chem 252:8040–8044

    Google Scholar 

  • Dardenne M, Pleau JM, Savino V, Bach JF (1982) Monoclonal antibody against the serum thymic factor (FTS). Immunol Lett 4:79–83

    Google Scholar 

  • Drenckhahn D, Gröschel-Stewart U (1980) Localization of myosin, actin and tropomyosin in rat intestinal epithelium: Immunohistochemical studies at the light and electron microscopical levels. J Cell Biol 86:475–482

    Google Scholar 

  • Ewijk W van, Rouse RV, Weissman IL (1980) Distribution of H-2 microenvironment in the mouse thymus. Immunoelectron microscopic identification of I-A and H2K bearing cells. J Histochem Cytochem 28:1089–1099

    Google Scholar 

  • Gad P, Clark SL (1968) Involution and regeneration of the thymus in mice, induced by bacterial endotoxin and studied by quantitative histology and electron microscopy. Am J Anat 122:573–606

    Google Scholar 

  • Gaudecker Bv. (1986) The development of the human thymus microenvironment. In: Müller-Hermelink HK (ed) The human thymus. Histophysiology and pathology. Current Topics in Pathology, Vol. 75, Springer, Berlin Heidelberg New York Tokyo, pp 1–41

    Google Scholar 

  • Gaudecker Bv., Müller-Hermelink HK (1980) Ontogeny and organization of the stationary non-lymphoid cells in the human thymus. Cell Tissue Res 207:287–306

    Google Scholar 

  • Gaudecker Bv., Schmale EM (1974) Similarities between Hassall's corpuscles of the human thymus and the epidermis. An investigation by electron microscopy and histochemistry. Cell Tissue Res 151:347–368

    Google Scholar 

  • Gaudecker Bv., Pfingsten U, Müller-Hermelink KH (1984) Localization and characterization of T-cell subpopulations and natural killer cells (HNK 1+ cells) in the human tonsilla palatina. An ultra-structural-immunocytochemical study. Cell Tissue Res 238:135–143

    Google Scholar 

  • Gelfand EW, Dosch HM, Shore A, Umatibul S, Lee JWW (1980) Role of the thymus in human T-cell differentiation. In: Gelfand WE, Dosch HM (eds) Biological basis of immunodeficiency disease. Raven, New York, pp 39–56

    Google Scholar 

  • Glauert AM, Glauert RH (1958) Araldite as an embedding medium for electron microscopy. J Biophys Biochem 4:191–194

    Google Scholar 

  • Hansmann ML, Radzun HJ, Kaiserling E, Parwaresch MR (1984) Immunoelectron microscopic demonstration of tissue antigens with monoclonal antibodies. Virchows Arch (Cell Pathol) 46:1–12

    Google Scholar 

  • Haynes BF (1984) The human thymic microenvironment. Adv Immunol 36:87–142

    Google Scholar 

  • Haynes BF, Shimizu K, Eisenbarth G (1983) Identification of human and rodent thymic epithelium using tetanus toxin and monoclonal antibody A2B5. J Clin Invest 71:9–14

    Google Scholar 

  • Janossy G, Thomas JA, Bollum FJ, Granger S, Pizzolo G, Bradstock KF, Wong L, McMichael A, Ganeshaguru K, Hoffbrand AV (1980) The human thymic microenvironment: An immunohistologic study. J Immunol 125:202–212

    Google Scholar 

  • Janossy G, Bofill M, Trejdosiewicz LK, Willox HNA, Chilosi M (1986) Cellular differentiation of lymphoid subpopulations and their microenvironment in the human thymus. In: Müller-Hermelink HK (ed) The thymus. Histophysiology and pathology. Current Topics in Pathology, Vol. 75, Springer, Berlin Heidelberg New York Tokyo, pp 89–125

    Google Scholar 

  • Jordan RK, Robinson JH (1981) T-lymphocyte differentiation. In: Kendall (ed) The thymus gland. Academic Press, London New York, pp 151–177

    Google Scholar 

  • Kater L, Oosterom R, McClure J, Goldstein AL (1979) Presence of thymosin-like factors in human thymic epithelium-conditioned medium. Int J Immunopharmacol 1:273–284

    Google Scholar 

  • Kruisbeek AM (1979a) Thymic factors and T-cell maturation in vitro: a comparison of the effects of thymic epithelial cultures with thymic extracts and thymus-dependent serum factors. Thymus 1:163–185

    Google Scholar 

  • Kruisbeek AM (1979b) Effect of factors in thymic epithelial culture supernatants (TES) on in vitro maturation of thymocytes. Ann NY Acad Sci 332:109–112

    Google Scholar 

  • Maagd RA de, MacKenzie WA, Schuurman HJ, Ritter MA, Price KM, Broekhuizen R, Kater L (1985) The human thymus microenvironment: Heterogeneity detected by monoclonal antiepithelial cell antibodies. Immunology 54:745–754

    Google Scholar 

  • McFarland EJ, Scearce RM, Haynes BF (1984) The human thymic micro-environment cortical thymic epithelium is an antigenically distinct region of the thymic microenvironment. J Immunol 133:1241–1249

    Google Scholar 

  • Monier JC, Dardenne M, Pleau JM, Schmitt D, Deschaux P, Bach JF (1980) Characterization of facteur thymique sérique (FTS) in the thymus. I. Fixation of anti-FTS antibodies on thymic reticulo-epithelial cells. Clin Exp Immunol 42:470–476

    Google Scholar 

  • Müller-Hermelink HK, Steinmann GG (1984) Age-related alterations of intrathymic microenvironment. In: de Weck AL (ed): Lymphoid cell functions in aging. Eurage Series No. III, pp 75–82

  • Müller-Hermelink HK, Marino M, Palestre G (1986) Pathology of thymic epithelial tumors. In: Müller-Hermelink HK (ed) The human thymus, histophysiology and pathology. Current Topics in Pathology, Vol. 75, Springer, Berlin Heidelberg New York Tokyo, pp 207–268

    Google Scholar 

  • Norris EH (1938) The morphogenesis and histogenesis of the thymus gland in man: In which the origin of the Hassall's corpuscles of the human thymus is discovered. Contrib Embryol 166:191–221

    Google Scholar 

  • Oosterom R, Kater L (1981a) The thymus in the aging individual. I. Mitogen responsiveness of human thymocytes. Clin Immunol Immunopathol 18:187–194

    Google Scholar 

  • Oosterom R, Kater L (1981b) The thymus in the aging individual. II. Thymic epithelial function in vitro in aging and in thymus pathology. Clin Immunol Immunopathol 18:195–202

    Google Scholar 

  • Plotnikoff NP, Murgo AJ, Faith RE (1984) Neuroimmunomodulation with encephalins: Effects on thymus and spleen weights in mice. Clin Immunol Immunpathol 32:52–56

    Google Scholar 

  • Pyke KW, Gelfand EW (1974) Morphological and functional maturation of human thymic epithelium in culture. Nature 251:421–423

    Google Scholar 

  • Radzun HJ, Parwaresch MR (1983) Differential immunohistochemical resolution of the human mononuclear phagocyte system. Cell Immunol 82:174–183

    Google Scholar 

  • Ritter MA, Sauvage CA, Cotmore SF (1981) The human thymus microenvironment: In vivo identification of thymic nurse cells and other antigenically-distinct subpopulations of epithelial cells. Immunology 44:439–446

    Google Scholar 

  • Schmitt D, Monier JC, Dardenne M, Pleau JM, Deschaux P, Bach JF (1980) Cytoplasmic localization of FTS (facteuer thymique sérique) in thymic epithelial cells. An immunoelectron-microscopical study. Thymus 2:177–186

    Google Scholar 

  • Schmitt D, Monier JC, Dardenne M, Pleau JM, Bach JF (1982) Location of FTS (facteur thymique sérique) in the thymus of normal and auto-immune mice. Thymus 4:221–231

    Google Scholar 

  • Singh J (1981) The ultrastructure of epithelial reticular cells. In: Kendall MD (ed) The thymus gland. Academic Press, London New York, pp 133–150

    Google Scholar 

  • Stein H, Bonk A, Tolksdorf G, Lennert K, Rodt H, Gerdes J (1980) Immunohistologic analysis of the organization of normal lymphoid tissue and non-Hodgkin's lymphomas. J Histochem Cytochem 28:746–760

    Google Scholar 

  • Steinmann GG (1984) Altersveränderungen des menschlichen Thymus. Habilitationsschrift. Med. Fak, Kiel

  • Steinmann GG (1986) Changes of the human thymus during aging. In: Müller-Hermelink HK (ed) The human thymus. Histophysiology and pathology. Current Topics in Pathology, Vol. 75, Springer, Berlin Heidelberg New York Tokyo, pp 43–88

    Google Scholar 

  • Steinmann GG, Müller-Hermelink HK (1984) Lymphocyte differentiation and its microenvironment in the human thymus during aging. Monogr Dev Biol 17:142–155

    Google Scholar 

  • Tweel JG van den, Taylor CR, McClure J, Goldstein AL (1979) Detection of thymosin in thymic epithelial cells by an immunoperoxydase method. Adv Exp Med Biol 114:511–515

    Google Scholar 

  • Ugolini V, Nunez G, Smith RG, Stastny P, Cappa JD (1981) Initial characterization of monoclonal antibodies against human monocytes. Proc Nat Acad Sci USA 77:6764–6768

    Google Scholar 

  • Weissman JL, Rouse RV, Kyewski BA, Lepault F, Butscher EC, Kaplan HS, Scollay RG (1982) Thymic lymphocyte maturation in the thymic microenvironment. Behring Inst Mitt 70:242–251

    Google Scholar 

  • Wekerle H, Ketelsen UP (1980) Thymic nurse cells — Ia-bearing epithelium involved in T-lymphocyte differentiation. Nature 283:402–404

    CAS  PubMed  Google Scholar 

  • Wekerle H, Ketelsen UP, Ernst M (1980) Thymic nurse cells. Lymphoepithelial cell complexes in murine thymuses: Morphological and serological characterization. J Exp Med 151:925–944

    Google Scholar 

  • Wijngaert FP van de, Rademakers LHPM, Schuurman HJ, de Weger RA, Kater L (1983) Identification and in situ localization of the “Thymic Nurse Cell” in man. J Immunol 130:2348–2351

    Google Scholar 

  • Wijngaert FP van de, Kendell MD, Schuurman HJ, Rademakers LHPM, Kater L (1984) Heterogeneity of epithelial cells in the human thymus. Cell Tissue Res 237:227–237

    Google Scholar 

  • Wilson MB, Nakane PK (1978) Recent developments in the periodate method of conjugating horseradish peroxidase (HRPO) to antibodies, immunofluorescence and related staining techniques. In: Knopp E, Holubar K, Wicks G (eds) Amsterdam Elsevier/North Holland Biomedical Press, Amsterdam, pp 215

    Google Scholar 

  • Zinkernagel RM (1979) The thymus: its influence on recognition of self major histocampatibility antigens by T-cells and consequences for reconstitution of immuno deficiency. In: Cooper MD, Lawton AR, Milscher PA, Mueller-Eberhard HJ (eds) Immune deficiency. Springer, Berlin Heidelberg New York, pp 171–181

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Anatomisches Institut der Universität Kiel, Bundesrepublik Deutschland

    Brita von Gaudecker

  2. Pathologisches Institut der Universität Kiel, Bundesrepublik Deutschland

    Gerhard G. Steinmann & Martin Leo Hansmann

  3. Immunologisches Institut der Universität Kiel, Bundesrepublik Deutschland

    Joachim Harpprecht

  4. Faculty of Medicine, Institute of Histology, Beograd, Yugoslavia

    Novica M. Milicevic

  5. Pathologisches Institut der Universität Würzburg, Bundesrepublik Deutschland

    Hans Konrad Müller-Hermelink

Authors
  1. Brita von Gaudecker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gerhard G. Steinmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin Leo Hansmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joachim Harpprecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Novica M. Milicevic
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This investigation was supported by grants from the Deutsche Forschungsgemeinschaft, and its Sonderforschungsbereich 111

Fellow of the Alexander von Humbold-Stiftung, Institute of Pathology, University of Würzburg, Federal Republic of Germany

The authors appreciate the contribution of human thymus tissue from Professor Alexander Bernhard, Abteilung kardiovasculäre Chirurgie der Universität Kiel; the gift of monoclonal antibodies from Dr. M.J.D. Anderson, Dr. M. Dardenne and Dr. H.J. Radzun; and the excellent technical assistence of Mrs. O.M. Bracker, Mrs. H. Hansen, Mrs. R. Köpke, Mrs. M. v. Kolszynski, Mrs. J. Quitzau, Mrs. H. Siebke, and Mrs. H. Waluk

Rights and permissions

Reprints and permissions

About this article

Cite this article

von Gaudecker, B., Steinmann, G.G., Hansmann, M.L. et al. Immunohistochemical characterization of the thymic microenvironment. Cell Tissue Res. 244, 403–412 (1986). https://doi.org/10.1007/BF00219216

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00219216

Key words

Search

Navigation