Summary
Lymphoepithelial complexes known as thymic “nurse” cells (TNC) have been isolated and described in the thymus of several animal species including man. Most of the investigations on TNC have been carried out in enzymatically digested thymuses in which TNC were isolated by differential sedimentation. In the present study we demonstrate TNC in immunohistochemically stained sections of human thymus as ring-shaped cells completely enclosing thymocytes and localized not only in the cortex, but also at the corticomedullary junction where they have not been previously described. TNC expressed epithelial markers [low and high molecular weight keratins identified by 35βH11 and 34βE12 monoclonal antibodies, a cortical antigen shared with neuroectodermal neoplasms recognized by the GE2 monoclonal antibody, and tissue polypeptide antigen (TPA:B1)], class II histocompatibility antigens (HLA-DR), and thymosin α1. Double staining experiments with the nuclear proliferation-associated antigen Ki-67 and the cortical epithelium marker GE2 showed that most thymocytes enclosed in these cortical TNC were not proliferating. The antigens expressed by TNC indicate that not only cortical, but also medullary epithelial cells are part of the TNC system. The possible role of TNC in the education and maturation of thymocytes is discussed.
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Berrih S, Arenzana-Seisdedos F, Cohen S, Devos R, Charron D, Virelizier J-L (1985) Interferon-γ modulates HLA class II antigen expression on cultured human thymic epithelial cells. J Immunol 135:1165–1171
Boyd RL, Oberhuber G, Hala K, Wick G (1984) Obese strain (OS) chickens with spontaneous autoimmune thyroiditis have a deficiency in thymic nurse cells. J Immunol 132:718–724
Chilosi M, Iannucci A, Menestrina F, Lestani M, Scarpa A, Bonetti F, Fiore-Donati L, Dipasquale B, Pizzolo G, Palestro G, Tridente G, Janossy G (1987) Immunohistochemical evidence of active thymocyte proliferation in human thymoma. Its possible role in the pathogenesis of autoimmune diseases. Am J Pathol 128:464–470
De Maagd RA, Mackenzie WA, Schuurman HJ, Ritter MA, Price KM, Broekhuizen R, Kater L (1985) The human thymus microenvironment: heterogeneity detected by monoclonal anti-epithelial cell antibodies. Immunology 54:745–754
de Waal Malefijt R, Leene W, Roholl PJM, Wormmeester J, Hoeben KA (1986) T cell differentiation within thymic nurse cells. Lab Invest 55:25–34
Dipasquale B, Colombatti M, Tridente G (1990) Morphological heterogeneity and phenotype modifications during long-term in vitro cultures of six new human glioblastoma cell lines. Tumori 76:172–178
Ennas MG, Chilosi M, Scarpa A, Lantini MS, Cadeddu G, Fiore-Donati L (1989) Isolation of multicellular complexes of follicular dendritic cells and lymphocytes: immunophenotypical characterization, electron microscopy and culture studies. Cell Tissue Res 257:9–15
Geenen V, Defresne MP, Robert F, Legros JJ, Franchimont P, Boniver J (1988) The neurohormonal thymic microenvironment: immunocytochemical evidence that thymic nurse cells are neuroendocrine cells. Neuroendocrinology 47:365–368
Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715
Gown AM, Vogel AM (1984) Monoclonal antibodies to human intermediate filament proteins. II. Distribution of filament proteins in normal human tissues. Am J Pathol 114:309–321
Hiramine C, Hojo K, Koseto M, Nakagawa T, Mukasa A (1990) Establishment of a murine thymic epithelial cell line capable of inducing both thymic nurse cell formation and thymocyte apoptosis. Lab Invest 62:41–54
Hirokawa K, McClure JE, Goldstein AL (1982) Age-related changes in localization of thymosin in the human thymus. Thymus 4:19–29
Kyewski BA (1986) Thymic nurse cells: possible sites of T-cell selection. Immunol Today 7:374–379
Kyewski BA, Kaplan HS (1982) Lymphoepithelial interactions in the mouse thymus: phenotypic and kinetic studies on thymic nurse cells. J Immunol 128:2287–2294
Leene W, Waal Malefijt R de, Roholl PJM, Hoeben KA (1988) Lymphocyte depletion in thymic nurse cells: a tool to identify in situ lympho-epithelial complexes having thymic nurse cell characteristics. Cell Tissue Res 253:61–68
McFarland EJ, Scearce RM, Haynes BF (1984) The human thymic microenvironment: cortical thymic epithelium is an antigenically distinct region of the thymic microenvironment. J Immunol 133:1241–1249
Mellerick DM, Osborn M, Weber K (1990) On the nature of serological tissue polypeptide antigen (TPA); monoclonal keratin 8, 18, and 19 antibodies react differently with TPA prepared from human cultured carcinoma cells and TPA in human serum. Oncogene 5:1007–1017
Muller-Hermelink HK, Marino M, Palestro G, Schumacher U, Kirchner T (1985) Immunohistological evidence for cortical and medullary differentiation in thymoma. Virchows Arch [A] 408:143–161
Nathrath WBJ, Heidenkummer P, Bjorklund V, Bjorklund B (1985) Distribution of tissue polypeptide antigen (TPA) in normal human tissues: immunohistochemical study on unfixed, methanol-, ethanol-, and formalin-fixed tissues. J Histochem Cytochem 33:99–109
Ramson J, Fischer M, Mercer L, Zlotnik A (1987) Lymphokinemediated induction of antigen-presenting ability in thymic stromal cells. J Immunol 139:2620–2628
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
Schnegg JF, Diserens AC, Carrel S, Accolla RS, Tribolet N de (1981) Human glioma-associated antigens detected by monoclonal antibodies. Cancer Res 41:1209–1213
Toussaint-Demylle D, Scheiff JM, Haumont S (1990) Thymic nurse cells: morphological study during their isolation from murine thymus. Cell Tissue Res 261:115–123
Tridente G, Riviera AP, Dipasquale B, Marcon C, Rocca M, Chilosi M, Gerosa M (1986) Antigen sharing by glioma cells and the epithelial thymus as revealed by the GE2 monoclonal antibody. In: Gerosa M, Rosemblum ML, Tridente G (eds) Brain tumors: biopathology and therapy. Pergamon Press, Oxford, 58:45–48
Tsunoda R, Kojima M (1987) A light microscopical study of isolated follicular dendritic cell-clusters in human tonsils. Acta Pathol Jpn 37:575–585
Vliet E van, Melis M, Ewijk W van (1984) Immunohistology of thymic nurse cells. Cell Immunol 87:101–109
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
Wekerle H, Ketelsen UP (1980) Thymic nurse cells — Ia-bearing epithelium involved in T-lymphocyte differentiation? Nature 283:402–404
Wijngaert FP van de, Kendall MD, Schuurman HJ, Rademakers LHPM, Kater L (1984) Heterogeneity of epithelial cells in the human thymus. An ultrastructural study. Cell Tissue Res 237:227–237
Wijngaert FP van de, Rademakers LHPM, Schuurman H, Weger RA de, Kater L (1983) Identification and in situ localization of the “thymic nurse cell” in man. J Immuno 130:2348–2351
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Dipasquale, B., Tridente, G. Immunohistochemical characterization of nurse cells in normal human thymus. Histochemistry 96, 499–503 (1991). https://doi.org/10.1007/BF00267075
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DOI: https://doi.org/10.1007/BF00267075