The Thymic Epithelial Cells

Immunohistochemical studies using specific antisera to a number of well-characterized thymic polypeptides have confirmed that it is the thymic epithelial cells that are the major hormone-producing cells of the thymus. Although most thymic polypeptides are found in both medullary and subcap-sular cortical epithelial cells, some are produced almost exclusively by epithelial cells localized in the subcapsular region (Hirokawa et al., 1982) (Fig. 5). The precise cells of origin for each of the well-characterized thymic polypeptides will be discussed in detail later in this article (see Section 6). 

Lymphoid Elements. The thymus plays a central role in the differentiation of T lymphocytes (Cantor and Weissman, 1976), and although much recent emphasis has focused on the thymic epithelial cells, it must be emphasized that the thymus is a lymphoid structure composed predominantly of thymic lymphocytes or thyntocytes. The thymus can be viewed as a solid epithelial organ, penetrated by blood vessels and infiltrated with thymocytes in four discrete areas the subcapsular cortex, the inner cortex, the medulla, and the perivascular connective tissue. 

The cells of origin of thymopoietin appear to be the thymic epithelial cells. By the use of a heteroantiserum and immunofluorescent techniques, the peptide was shown to localize to thymic epithelial cells (Goldstein, 1977). In more recent studies it has been demonstrated that both the subcapsular cortical as well as the medullary thymic epithelial cells react with antithymopoietin antibodies (Haynes, 1984). A molecule that is indistinguishable from thymopoietin by immunoassay is also present in one major extra-thymic site, the epidermis. Two to fifteen percent of human epidermal cells appear to endogenously produce thymopoietin in tissue culture. These cells have been characterized as basal keratinocytes of the epidermis (Chu et al., 1983). 

Comments MG nsnally can be very well treated, bnt it reqnires a coordinated effort and very careful monitoring. Slightly increased tendon reflexes are typical of MG. Removal of the thymoma eliminates the thymic epithelial cells that possess nicotinic receptors [5], which we have proposed to be the provoking origin of the MG dysimmune mechanism [4], possibly from viral infection of them. 

Pieters RHH, Albers R, Bleumink R, SnoeiJ NJ, Itoh T, Seinen W, Penninks AH (1995) The thymus atrophy-inducing organotin compound DBTC inhibits the binding of thymocytes to thymic epithelial cells. International Journal of Immunopharmacology, 17(4) 329-337. 

Klein L Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self Nat Immunol 2001 2 1032-1039. 

In addition to the three major classes of APCs (Table 1.7) already described, a number of other cells including fibroblasts, thyroid epithelial cells, thymic epithelial cells, glial cells, endothelial cells (vascular) and pancreatic (3 cells can be induced to present antigens to T cells. These cells do not constitutively express MHC class... 

Non-professional APCs do not constitutively express the MHC proteins required for interaction with naive T-cells these are expressed only upon stimulation of the non-professional APC by certain cytokines, such as IFN-y (interferon-gamma). Non-professional APCs include fibroblasts (skin), thymic epithelial cells, thyroid epithelial cells, ghal cells (brain), pancreatic... 

Tumors that may be confused with CUPS within the mediastinum include thymic neoplasm (thymoma, thymic carcinoid, or thymic carcinoma), thyroid tumors, lymphomas, paragangliomas, and germ cell tumors. Thymomas are generally easy to recognize owing to their characteristic admixture of neoplastic thymic epithelial cells with non-neoplastic lymphocytes. The neoplastic thymic epithelial cells are positive for keratins,... 

The most helpful immunostain in this differential diagnosis—and one that the author, through regrettable mistakes, has made routine—is an assessment of keratin reactivity. The elaborately interconnecting epithelial cells of lymphocyte-predominant thymoma (LPT), which are not seen in LL, are distinctive. This pattern is essential to differential diagnosis, because LL and other lymphomas of thymus may demonstrate entrapped non-neoplastic thymic epithelial cells that are visible (but widely separated and non-interconnecting) on keratin immunostains. 3 Another potential marker for thymic epithelium—p63 protein" —is not as useful in this particular contextual setting. That is true because LL may be p63-reactive as well." ... 

The elaborate keratin-positive meshwork of thymic epithelial cells is present in thymoma, but not in areas of thymic hyperplasia or lymphoma. 

Yu GH, Salhany KE, Gokaslan ST, et al. Thymic epithelial cells as a diagnostic pitfall in the fine needle aspiration diagnosis of primary mediastinal lymphoma. Diagn Cytopathol. 1997 16 460-465. 

Thymomas may occur in the pleura and can be confused with mesothelioma. These neoplasms may be confused with a sarcomatoid mesothelioma with a heavy lymphoid infiltrate or with a lymphohistiocytoid mesothelioma. None of the cases presented by Moran and coworkers showed radiographic evidence of a mediastinal tumor, however 6 cases showed histologic features of a mixed (lymphocyte-epithelial) thymoma. The neoplastic thymic epithelial cells express keratin and CD5. 

The interaction between lymphocytes found within the thymus (thymocytes) and the epithelial elements of the thymic stromal tissue was first suggested by Maximow (1909), who observed that the thymic epithelium seemed to attract lymphoid wandering cells and to induce their proliferation in that organ. However, it was not until the past two decades that we have begun to understand the complex biochemical events by which the thymus exerts its influence on the immune system. It is now established that thymic epithelial cells have the capacity for synthesizing and secreting a variety of maturation-differentiation-inducing polypeptides and that the... 

In this chapter we will review the anatomy and physiology of the thymus gland as currently conceived. We will pay particular attention to the variety of polypeptides that are produced by thymic epithelial cells and that have been well characterized biochemically. Finally, we will discuss the various primary and secondary immunodeficiency disorders that are associated with abnormalities of the endocrine thymus. 

Numerous ultrastructural and histochemical studies have now demonstrated conclusively that many of the epithelial cells in the thymus have the characteristics of secretory cells (Singh, 1981). Cortical as well as medullary thymic epithelial cells may exhibit membrane-bound, electron-dense granules, which are also found in a variety of endocrine organs. Epithelial cells containing membrane-bound, electron-dense granules have now been identified in avian (Frazier, 1973 Hakason et al., 1974 Kendall and Frazier,... 

Fig. 5. Thymic epithelial cells. Both the superficial cortical and medullary thymic epithelial cells of this infimt s thymus gland stain positively with an immunofluorescent antibody to thymosin oi. [From Goldstein et al. (1981). With permission of Academic Press.]...

Although it appears that the key microenvironmental influence in the embryonic thymus derives from its epithelial cells, other nonlymphoid cells are present early in gestation in the thymus, which may possess important inductive capabilities for thymocytes including the thymic nurse cell, thymic macrophages, and interdigitating reticulum cells (see Sections 4.2.1.6-4.2.1.8). 

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