Summary
The thymus develops from a paired epithelial anlage in the neck. This review considers how ectoderm (vesicula cervicalis) and endoderm (third pharyngeal pouch) contribute to the epithelial stroma of the thymus. Stromal elements of mesodermal origin are capillaries, septae and perivascular spaces and single invading cells. These elements separate the thymus into pseudolobuli. The thymus epithelial space and the perivascular spaces are always separated from each other by a closed, flat epithelial cell layer, with a basal lamina which contributes to the blood-thymus barrier. From the 9th gestational week, prethymic precursor cells from hemopoietic centers, begin to invade the thymus anlage. There they finally mature to committed post-thymic T cells. The thymus microenvironment of postnatal thymus is composed of six different types of epithelial cells and several stromal cells of mesodermal origin. The location of these diverse stationary cells is described, and their functional significance is discussed. Obviously these stromal cell types have a special function in providing the proper environment for T-cell maturation. The function of the thymus includes the maturation and/or selection of antigen specific T-cells. The main issue of intra-thymic T-cell differentiation is the development and expression of T-cell-antigen receptors. The great diversity of these receptors is generated by a rearrangement of the T-cell-receptor-genes in order to furnish the host with a mature T-cell repertoire that is capable of recognizing the world of extrinsic antigens. In a synopsis the manyfold interrelationships between the thymus microenvironment and the developing thymocytes are summarised.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Abbreviations
- BALT :
-
Bronchus Associated Lymphoid Tissue
- CD :
-
Cluster of Differentiation
- cCD3 :
-
cytoplasmic CD3
- mCD3 :
-
membranous CD3
- C.R. :
-
Crown Rump
- GALT :
-
Gut Associated Lymphoid Tissue
- HLA :
-
Human Leucocyte antigen
- HLA-DR :
-
Gene product of the MHC-class II (this antigen is a surface molecule of numerous stationary and free cells of the immune system)
- IDC :
-
Interdigitating Cell
- IL1 :
-
Interleukin 1 (cytokine derived mainly from makrophages, but also from other cell types)
- IL2 and IL4 :
-
Interleukin 2 and 4 (cytokines derived mainly from T-cell, but also from other cell types)
- IL4R :
-
Interleukin 4-Receptor
- Mab :
-
Monoclonal antibody
- MHC :
-
Major Histocompatibility Complex
- p.c. :
-
post conception
- TCR :
-
T-Cell-Receptor
- TNC :
-
Thymic Nurse Cell
- TdT :
-
Terminal deoxynucleotidyl Transferase
References
Bargmann W (1943) Der Thymus. In: von Möllendorf W (ed) Blutgefäß- und Lymphgefäßapparat. Innersekretorische Drüsen. (Handbuch der mikroskopischen Anatomie des Menschen Bd. 6/7). Springer, Berlin, pp 1–172
Beller DI, Unanue ER (1979) Evidence that thymocytes require at least two distinct signals to proliferate. J Immunol 123:2890–2893
Bevan MJ (1977) In a radiation chimera host H-2 antigens determine the immune responsiveness of donor cytotoxic cells. Nature 269:417–418
Blanc F (1974) Contribution á l'étude de la microvascularisation du lobule thymique chez l'homme. Arch Anat Hist Embryol 57:29–60
Blanc F, Fabre M, Koritke JG (1973) Le thymus de nouvenau-né humain et ses espaces périvasculaires — étude ultrastructurale. Arch Anat Hist Embryol 56:223–242
Burnet FM (1959) The clonal selection theory of acquired immunity. Cambridge University Press, Cambridge
Campana D (1989) The developmental stages of the human T-cell receptors: a review. Thymus 13:3–18
Cordier AC, Haumont SA (1980) Development of thymus, parathyroids and ultimo-branchial bodies in NMRI and nude mice. Am J Anat 157:227–263
Dardenne M, Bach JF (1988) Functional biology of thymic hormones. In: Kendall MD, Ritter MA (eds) Thymus Update Vol 1. Harwood Academic Publishers, London Paris New York Melbourne, pp 101–116
Dargemont C, Dunon D, Deugnier MA, Denoyelle M, Girault JM, Lederer F, Ho Diep Lê K, Godeau F, Thiery JP, Imhof BA (1989) Thymotaxin, a chemotactic protein, is identical to β 2-Microglobulin. Science 246:803–806
Didierjean L, Saurat JH (1980) Epidermis and thymus. Similar antigenic proprties in Hassall's corpuscle and subsets of keratinocytes. Clin Exp Dermatol 5:395–404
Drenckhahn D, von Gaudecker B, Müller-Hermelink HK, Unsicker K, Gröschel-Stewart U (1979) Myosin- and actin-containing cells in the human postnatal thymus. Ultrastructural and immunohistochemical findings in normal thymus and in Myasthenia Gravis. Virchows Arch [B] 32:33–45
Dunon D, Kaufman J, Salomonsen J, Skjoedt K, Vainio O, Thiery JP, Imhof BA (1990) T-cell precursor migration toward β2-microglobulin is involved in thymus colonisation of chicken embryos. EMBO J (in press)
Ewijk W van (1988) Cell surface topography of thymic microenvironments. Lab Invest 59:579–590
Farr AG, Anderson SK, Marrak P, Kappler J (1985) Expression of antigen specific major histocompatibility restricted receptors by cortical and medullary thymocytes in situ. Cell 43:543–553
Fontaine-Pérus JC, Caiman FM, Kaplan C, le Douarin NM (1981) Seeding of the 10-day mouse embryo thymic rudiment by lymphocyte precursors in vitro. J Immunol 126:2310–2316
Gaudecker von B (1977) Die fortschreitende Erweiterung mesodermaler perivaskulärer Räume im Thymus des Menschen. Verh Anat Ges 71:783–787
Gaudecker von B (1986) The development of the human thymus micro-environment. In: Müller-Hermelink HK (ed) The human thymus. Histophysiology and Pathology. Curr Top Pathol 75. Springer, Berlin Heidelberg New York Tokyo, pp 1–41
Gaudecker von B, Müller-Hermelink HK (1980) Ontogeny and organization of the stationary non-lymphoid cells in the human thymus. Cell Tissue Res 207:287–306
Gaudecker von B, Müller-Hermelink HK (1982) Ultrastructural investigation of the Lympho-epithelial and Lympho-mesenchymal interactions in the ontogeny of the human thymus. In: Fabris N (ed) Immunology and ageing. Martinus Nijhoff, The Hague Boston London, pp 51–58
Gaudecker von B, 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
Gaudecker von B, Steinmann GG, Hansmann ML, Harpprecht J, Milicevic NM, Müller-Hermelink HK (1986) Immunohistochemical characterization of the thymic micro-environment. Cell Tissue Res 244:403–412
Gaudecker von B, Larché M, Schuurman H-J, Ritter MA (1989) Analysis of the fine distribution of thymic epithelial microenvironment molecules by immuno-electron microscopy. Thymus 13:187–194
Good RA, Dalmasso AP, Martinez C, Archer OK, Pierce JC, Papermaster BW (1962) The role of the thymus in development of immunologic capacity in rabbits and mice. J Exp Med 116:773–796
Hamilton WJ, Boyd JD, Mossman HW (1972) Human embryology. Heffer, Cambridge; Williams & Wilkins, Baltimore
Hammar JA (1926) Die Menschenthymus in Gesundheit und Krankheit. I Das normale Organ. Z Mikrosk Anat Forsch Ergänzungsband 6:1–570
Haynes BF (1984) The human thymic micro-environment. Adv Immun 36:87–142
Hendrick SM (1989) T Lymphocyte Receptors. In: Paul WE (ed) Fundamental Immunology, Second Edition. Raven Press, New York, pp 291–313
Imhof BA, Deugnier MA, Bauvois B, Dunon D, Thiery JP (1989) Properties of pre-T cells and their chemotactic migration to the thymus. In: Kendall MD, Ritter MA (eds) Thymus Update. Vol 2. Harwood Academic Publishers, London Paris New York Melbourne, pp 3–19
Janossy G, Campana D (1989) Ontogeny of the human T cell receptors — single cell studies. In: Kendall MD, Ritter MA (eds) Thymus Update. Vol 2 Harwood Academic Publishers, London Paris New York Melbourne, pp 39–58
Jordan RK, Robinson JH (1981) T-Lymphocyte differentiation. In: Kendall MD (ed) The thymus gland. Academic Press, London New York, pp 151–177
Kendall MD (ed) (1981) The thymus gland. Academic Press, London
Kendall MD (1988) Anatomical and physiological factors influencing the thymic micro-environment. In: Kendall MD, Ritter MA (eds) Thymus Update. Vol 1. Harwood Academic Publishers, London Paris New York Melbourne, pp 27–65
Kendall MD, Schuurman HJ, Fenton J, Broekhuizen R, Kampinga J (1988) Implantation of cultured thymic fragments in congenitally athymic (nude) rats. Cell Tissue Res 254:283–294
Knapp W, Rieber P, Dörken B, Schmidt RE, Stein H, Borne AEG (1989) Immunology Today 10:253–258
Lampert IA, Ritter MA (1988) The origin of the diverse epithelial cells of the thymus: is there a common stem cell? In: Kendall MD, Ritter MA (eds) Thymus Update. Vol 1. Harwood Academic Publishers London Paris New York Melbourne, pp 5–25
Larché M, Ritter MA (1989) IL-4, Ontogenesis and the thymus. In: Kendall MD, Ritter MA (eds) Thymus Update, Vol. 2. Harwood Academic Publishers, London Paris New York Melbourne, pp 59–72
Lechler RI (1989) Rearrangement and expression of T cell receptor genes and the selection of thymocytes. In: Kendall MD, Ritter MA (eds) Thymus Update. Vol 2. Harwood Academic Publishers, London Paris New York Melbourne, pp 21–38
LeDouarin NM, Jotereau FV (1975) Tracing of cells of the avian thymus through embryonic life in interspecific chimeras. J Exp Med 142:17–40
LeDouarin NM, Jotereau FV (1980) Homing of lymphoid stem cells to the thymus and the bursa of Fabricius studied in avian embryo chimaeras. In: Fougereau M, Dausset J (eds) Immunology 80. Academic Press, London New York, pp 285–302
LeDouarin NM, Jotereau FV (1981) The ontogeny of the thymus. In: Kendall MD (ed) The Thymus Gland. Academic Press, London New York, pp 133–155
LeDouarin NM, Dieterlen-Liévre F, Oliver PD (1984) Ontogeny of primary lymphoid organs and lymphoid stem cells. Am J Anat 170:261–299
Lindstrom J (1979) Autoimmune response to acetylcholine receptor in myasthenia gravis and its animal model. Adv Immunol 27:1–50
Maagd RA de, 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
Moore MAS, Owen JJT (1967) Experimental studies on the development of the thymus. J Exp Med 126:715–726
Mosmann TR, Bond MW, Coffman RL, Ohara T, Paul WE (1986) T-cell and mast cell lines respond to B-cell stimulatory factor-1. Proc Natl Acad Sci USA 83:5654–5658
Nakahama M, Mori N, Mori S, Shindo G, Yokoi Y, Machinami R (1990) Immunohistochemical and histometrical studies of the human thymus with special emphasis on age-related changes in medullary epithelial and dendritic cells. Virchows Archiv [B] 58:245–251
Nieuwenhuis P, Stet RJM, Wagenaar JPA, Wubbena AS, Kampinga J, Karrenbeld A (1988) The transcapsular route: a new way for (self) antigens to by-pass the blood-thymus barrier? Immunology Today 9:372–375
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
Owen JJT, Ritter MA (1969) Tissue interaction in the development of thymus lymphocytes. J Exp Med 129:431–442
Paliard X, de Waal Malefijt R, de Vries JE, Spits H (1988) Interleukin-4 mediates CD8 induction on human CD4+ T-cell clones. Nature 335:642–644
Raviola E, Karnovsky MJ (1972) Evidence for a blood-thymus barrier using electron-opaque tracers. J Exp Med 136:466–497
Reinherz EL, Kung PC, Goldstein G, Levey RH, Schlossman SF (1980) Discrete stages of human intrathymic differentiation: Analysis of normal thymocytes and leukaemic lymphoblasts of T-cell lineage. Proc Natl Acad Sci USA 77:1588–1592
Ritter MA, Sauvage CA, Cotmore SF (1981) The human thymus micro-environment in vitro identification of the thymic nurse cells and other antigenetically-distinct subpopulations of epithelial cells. Immunology 44:439–446
Sha WC, Nelson CA, Newberry RD, Kranz DM, Russel JH, Loh DY (1988) Positive and negative selection of an antigen receptor on T-cells in transgenic mice. Nature 336:73–76
Schmitt D, Monier YC, Dardenne M, Pleau YM, Bach YF (1982) Location of FTS (facteur thymique sérique) in the thymus of normal and auto-immune mice. Thymus 4:221–231
Stein H, Müller-Hermelink HK (1977) Simultaneous presence of receptors for complement and sheep red blood cells on human fetal thymocytes. Br J Haematol 36:225–230
Steinmann GG (1986) Changes of the human thymus during aging. In: Müller-Hermelink HK (ed) The Human Thymus. Histophysiology and Pathology. Curr Top Pathol Vol 75, Springer, Berlin Heidelberg New York Tokyo, pp 43–88
Stutman O (1982) A model for T-cell differentiation. In: Fabris N (ed) Immunology and ageing. Nijhof, The Hague, pp 3–16
Stutman O, Good RA (1971) Immune competence of cells derived from hemopoietic liver after traffic to thymus. In: Lindahl-Kiessling K, Alm G, Hanna MG (eds) Plenum Press, New York, pp 129–133
Wekerle H, Müller-Hermelink HK (1986) The thymus in myasthenia gravis. In: Müller-Hermelink HK (ed) The Human Thymus. Histophysiology and Pathology. Curr Top Pathol 75. Springer, Berlin Heidelberg New York Tokyo, pp 179–206
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
Wijngaert FP van der, Kendall MD, Schuurman HJ, Rademalers LHPM, Kater L (1984) Heterogeneity of epithelial cells in the human thymus. An ultrastructural study. Cell Tissue Res 237:227–237
Wilcox N, Schluep M, Ritter MA, Schuurman HJ, Newsom-Davis J, Christensson B (1987) Myasthenic and nonmyasthenic thymoma. An expansion of a minor cortical epithelial cell subset? Am J Pathol 127:447–460
Zinkernagel RM (1979) The thymus: its influence on recognition of self major histocompatibility antigens by T-cells and consequences for reconstitution of immuno deficiency. In: Cooper MD, Lawton AR, Milscher PA, Mueller-Eberhard HJ (eds) Immunodeficiency. Springer, Berlin Heidelberg New York, pp 171–181
Zinkernagel RM, Callahan GN, Althage A, Cooper S, Klein PA, Klein J (1978a) On the thymus in the differentiation of “H-2-self-recognition” by T-cells: evidence for dual recognition? J Exp Med 147:882–896
Zinkernagel RM, Callahan GN, Althage A, Cooper S, Streilein JW, Klein J (1978b) The lymphoreticular system in triggering virus plus self-specific cytotoxic T-cells: evidence for T cell help. J Exp Med 147:897–911
Zinkernagel RM, Callahan GN, Klein J, Dennert G (1978c) Cytotoxic T-cells learn specificity for self-H-2 during differentiation in the thymus. Nature 271:251–253
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
von Gaudecker, B. Functional histology of the human thymus. Anat Embryol 183, 1–15 (1991). https://doi.org/10.1007/BF00185830
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00185830