Abstract
The thymic stroma is heterogeneous with regard to cellular morphology and cellular function. In this study, we employed the monoclonal antibody ER-TR4 to characterize stromal cells at the ultrastructural level. To identify the labelled cell type, we used two techniques: immunogold labelling on ultrathin frozen sections and immunoperoxidase staining on thick “vibratome” sections. ER-TR4 reacted with thymic Type 1 epithelial cells (according to our classification). A dense labelling appears in the cytoplasm of cortical cells using the two techniques. Immunogold labelling identified small cytoplasmic vesicles whereas the cytoplasm and the cell membrane seem to be labelled with the immunoperoxidase technique. ER-TR4 also identified isolated thymic nurse cells (TNC), and was observed in vitro to inhibit the capacity of some type 1 epithelial cells to establish interactions with immature thymocytes. This finding supports the hypothesis that the factor is involved in the formation of lymphoepithelial interactions within thymic nurse cells, and thus in the relations that immature thymocytes establish with the thymic microenvironment.
Similar content being viewed by others
References
Andrews P, Boyd RL (1985) The murine thymic nurse cell: an isolated thymic microenvironment. Eur J Immunol 15: 36–42
Carding SR, Hayday AC, Bottomly K (1991) Cytokines in T-cell development. Immunol Today 12: 239–245
De Waal Malefijt R, Leene W, Roholl P, Wormmeester J, Hoeben K (1986) T cell differentiation within thymic nurse cells. Lab Invest 55: 25–34
Defresne MP, Goffinet G, Boniver J (1986) In situ characterization in freeze-fractured mouse thymuses of lymphoepithelial complexes ultrastructurally similar to isolated thymic nurse cells. Tissue Cell 18: 321–330
Defresne MP, Humblet C, Rongy AM, Greimers R, Boniver J (1990) Effect of interferon-gamma and tumor necrosis factoralpha on lymphoepithelial interactions within thymic nurse cells. Eur J Immunol 20: 429–432
Deman J, Martin MT, Delvenne P, Humblet C, Boniver J, Defresne MP (1992) Analysis by in situ hybridization of cells expressing mRNA for tumor necrosis factor in the developing thymus of mice. Dev Immunol 2: 103–109
Duijvestijn A, Hoefsmit E (1981) Ultrastructure of the rat thymus. The microenvironment of T lymphocyte maturation. Cell Tissue Res 218: 279–282
Farr A, Nelson A, Twex J, Hosier S (1991) Epithelial heterogeneity in the murine thymus: a cell surface glycoprotein expressed by subcapsular and medullary epithelium. J Histochem Cytochem 39: 645–653
Fowlkes BJ, Pardoll DW (1989) Molecular and cellular events of T cell development. Adv Immunol 44: 207–264
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
Haynes B (1984) The human thymic microenvironment. Adv Immunol 36: 87–142
Haynes B, Shimizy K, Eisenbarth G (1983) Identification of human and rodent thymic epithelium using tetanus toxin and monoclonal antibody A2B5. J Clin Invest 71: 9–17
Hirokawa K, Utsuyama M, Morrizumi H, Handa S (1986) Analysis of the thymic microenvironment by monoclonal antibodies with special reference to thymic nurse cells. Thymus 8: 349–360
Houben-Defresne MP, Varlet A, Goffinet G, Boniver J (1982) Thymic nurse cells are the first site of virus replication after inoculation of the radiation leukemia virus. Leuk Res 6: 231–241
Kendall MD, Ritter MA, (eds) (1988) Thymus update, vol 1. The microenvironment of the human thymus. Harwood Academic Publishers, Switzerland
Kyewski BA (1991) 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
Kyewski BA, Rouse RV, Kaplan HS (1982) Thymocyte rosettes: multicellular complexes of lymphocytes and bone marrow derived cells in the mouse thymus. Proc Natl Acad Sci USA 79: 5646–5650
Marrack P, Brinster R, Palmiter R, Burkly L, Flavell R, Kappler J (1988) The effect of thymus environment on T cell development and tolerance. Cell 53: 627–634
Nabarra B, Andrianarison I (1987) Ultrastructural studies of thymic reticulum. I. Epithelial component. Thymus 9: 95–121
Nabarra B, Andrianarison I (1991) Ultrastructural studies of thymic reticulum. II. Non-epithelial component. Thymus 17: 39–61
Penninger J, Hala K, Wick G (1990) Intrathymic nurse cell lymphocytes can induce a specific graft-versus-host-reaction. J Exp Med 172: 521–529
Ramsdell F, Fowlkes BJ (1990) Clonal deletion versus clonal anergy — the role of the thymus in inducing self-tolerance. Science 248: 1342–1348
Rouse R, Bolin L, Bender J, Kyewski BA (1988) Monoclonal antibodies reactive with subsets of mouse and human thymic epithelial cells. J Histochem Cytochem 36: 1511–1517
Singer K (1990) Interactions between epithelial cells and T lymphocytes: role of adhesion molecules. J Leuk Biol 48: 367–374
Singer K, Denning S, Whichard L, Haynes B (1990) Thymocyte LFA-1 and thymic epithelial cell ICAM/1 molecules mediate binding of activated human thymocytes to thymic epithelial cells. J Immunol 144: 2931–2939
Stutman O (1978) Intrathymic and extrathymic cell maturation. Immunol Rev 422: 138–184
Tokuyasu KT (1973) A technique for ultracryotomy of cell suspensions and tissues. J Cell Biol 57: 551–565
Tokuyasu KT (1984) Immuno-cryoultramicrotomy. In: Polak JM, Varndell IM (eds) Immunolabelling for electron microscopy. Elsevier, Science Publishers, Amsterdam, pp 71–82
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
Van Ewijk W (1988) Cell surface topography of thymic microenvironments. Lab Invest 59: 579–590
Van Ewijk W (1989) Immunohistology of lymphoid and non lymphoid cells in the thymus in relation to T lymphocyte differentiation. Am J Anat 170: 311–330
Van Ewijk W (1991) T-cell differentiation is influenced by thymic microenvironments. Annu Rev Immunol 9: 591–615
Van Ewijk W, Coffman R, Weissman IL (1980a) Immunoelectron microscopy of cell surface antigen: a quantitative analysis of antibody binding after different fixation protocols. Histochem J 12: 349–358
Van Ewijk W, Rouse RV, Weissman IL (1980b) Distribution of H-2 microenvironments in the mouse thymus. J Histochem Cytochem 28: 1089–1099
Van Vliet E, Melis M, Van Ewijk W (1984) Monoclonal antibodies to stromal cell types of the mouse thymus. Eur J Immunol 14: 524–529
Van Vliet E, Melis M, Van Ewijk W (1984b) Immunohistology of thymic nurse cells. Cell Immunol 87: 101–109
Wekerle H, Ketelsen U, Ernst M (1980) Thymic nurse cells. Lymphoepithelial cell complexes in murine thymuses: morphological and serological characterization. J Exp Med 151: 925–944
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Defresne, MP., Van Vliet, E., Willemsen, R. et al. The ER-TR4 monoclonal antibody recognizes murine thymic epithelial cells (Type 1) and inhibits their capacity to interact with immature thymocytes: immuno-electron microscopic and functional studies. Histochemistry 101, 355–363 (1994). https://doi.org/10.1007/BF00268997
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00268997