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Homing of hemopoietic precursor cells to the fetal rat thymus: intercellular contact-controlled cell migration and development of the thymic microenvironment

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Abstract

Colonization of rat thymic anlage by the first wave of hemopoietic precursor cells (HPc) was investigated by means of transmission electron microscopy and immunocytochemistry. HPc began migration into the thymic anlage between 13 and 13.5 gestation days (GD), terminated colonization at about GD 16, and migrated sequentially through the two compartments of the thymic anlage under the control of typical populations of stromal cells. First, HPc migrated through the external compartment of the perithymic mesenchyme, tightly interconnected with fibroblasts. The type of junctions between the cells indicated that the fibroblasts played a role in the control of HPc trafficking and in their entrance to the epithelial compartment. The second stage of colonization was initiated by the entrance of HPc to the epithelial compartment and their interaction with thymic epithelial cells (TECs). Based on morphological criteria, two populations of HPc were distinguished that colonized the anlage at various stages of its development. The predominant population with ultrastructural traits common to thymocytes “homed” into the epithelial type primordium. A small number of HPc, identified by protein S-100 expression and by Birbeck’s granules as precursors of dendritic cells, colonized lymphoepithelial anlage in which subsets of cortical and medullary TECs could be distinguished. Thymocyte migration and their reciprocal interactions with cortical TECs differed from the trafficking of dendritic cells toward the medulla. The results demonstrated the influence of maturing thymocytes on the development of cortical epithelial cells and the dynamic organization of the medullary microenvironment with direct involvement of dendritic cells.

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References

  1. Alonso-C LM, Munoz JJ, Zapata AG (2000) Early T cell development can be traced in rat fetal liver. Eur J Immunol 30:3604–3613

  2. Alonso-C LM, Munoz JJ, Zapata AG (2001) Delineation of intrathymic T, NK, and dendritic cell (DC) progenitors in fetal and adult rats: demonstration of a bipotent T/DC intermediate precursor. J Immunol 167:3635–3641

  3. Alves LA, Nihei OK, Fontseca PC, Campos-de-Carvelho AC, Savino W (2000) Gap junction modulation by extracellular signaling molecules: the thymus model. Braz J Med Biol Res 33:457–465

  4. Anderson G, Jenkinson EJ, Moore NC, Owen JJ (1993) MHC class II-positive epithelium and mesenchyme cells are both required for T-cell development in the thymus. Nature 362:70–73

  5. Anderson G, Anderson KL, Tchilian EZ, Owen JJT, Jenkinson EJ (1997) Fibroblast dependency during early thymocyte development maps to the CD25+CD44+ stage and involves interactions with fibroblast matrix molecules. Eur J Immunol 27:1200–1206

  6. Ardavin C (1997) Thymic dendritic cells. Immunol Today 18:350–361

  7. Ardavin C, Wu L, Li C-L, Shortman K (1993) Thymic dendritic cells and T cells develop simultaneously within the thymus from a common precursor population. Nature 362:761–763

  8. Banwell CM, Partingon KM, Jenkinson EJ, Anderson G (2000) Studies on the role of IL-7 presentation by mesenchymal fibroblasts during early thymocyte development. Eur J Immunol 30:2125–2129

  9. Bendriss Vermare N, Barthelemy C, Durand I, Bruand C, Dezutter-Dambuyant C, Moulian N, Berrih-Aknin S, Caux C, Trinchieri G, Briere F (2001) Human thymus contains IFN-alpha-producing CD11c(-), myeloid CD11c(+), and mature interdigitating dendritic cells.J Clin Invest 107:835–844

  10. Bleul CC, Boehm T (2001) Chemokines define distinct microenvironments in the developing thymus. Eur J Immunol 30:3371–3379

  11. Bockman DE, Kirby ML (1984) Dependence of thymic development on derivatives of the neural crest. Science 223:498–499

  12. Brelińska R, Kaczmarek E, Warchoł JB, Jaroszewski J (1985) Distribution of different cell types within the rat thymus in the neonatal period of life. Cell Tissue Res 240:473–478

  13. Brelińska R, Ostalska D, Paczkowska A, Jaroszewski J (2001) Histogenesis of the rat thymic medulla during the first stages of development. Folia Histochem Cytobiol 39:197–198

  14. Brelińska R, Ostalska D, Kaczmarek E, Kowalska K (2002) Stages of the rat thymic medulla development in foetal period. Folia Histochem Cytobiol 40:171–172

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

  16. De Yébenes VG, Carrasco YR, Ramiro AR, Toribio ML (2002) Identification of a myeloid intrathymic pathway of dendritic cell development marked by expression of granulocyte macrophage-colony-stimulating factor receptor. Blood 99:2948–2956

  17. Duijvestijn AM, Sminia T, Köhler YG, Janse EM, Hoefsmit ECM (1984) Ontogeny of rat thymus micro-environment: development of the interdigitating cell and macrophage populations. Dev Comp Immunol 8:451–460

  18. Ewijk W van , Wang B, Hollander G, Kawamoto H, Spanopoulou E, Itoi M, Amagai T, Jiang Y-F, Germeraad WTV, Chen W-F, Katsura Y (1999) Thymic microenvironments, 3-D versus 2D? Semin Immunol 11:57–64

  19. Farr A, Hosier S, Nelson A, Itohara S, Tonegawa S (1990) Distribution of thymocytes expressing gamma delta receptors in the murine thymus during development. J Immunol 144:492–498

  20. Hollander GA, Wang B, Nichogiannopoulou A, Platenburg PP, Ewijk W van, Burakoff SJ, Gutierrez-Ramos JC, Terhorst C (1995) Developmental control point in induction of thymic cortex regulated by a subpopulation of prothymocytes. Nature 373:350–353

  21. Iizuka T, Tanaka T, Suematsu M, Miura S, Watanabe T, Koike R, Ishimura Y, Ishii H, Miyasaka N, Miyasaka M (2000) Stage-specific expression of mucosal addressin cell adhesion molecule-1 during embryogenesis in rats. J Immunol 164:2463–2471

  22. Itoi M, Kawamoto H, Katsura Y, Amagai T (2001) Two distinct steps of immigration of hematopoietic progenitors into the early thymus anlage. Int Immunol 13:1203–1211

  23. Jotereau FV, Heuze F, Saloman-Vie V, Gascan H (1987) Cell kinetics on the fetal mouse thymus: precursor cell input, proliferation and emigration. J Immunol 138:1026–1030

  24. Kawakami N, Nishizawa F, Sakane N, Iwao M, Tsujikawa K, Ikawa M, Okabe M, Yamamoto H (1999) Roles of integrins and CD44 on the adhesion and migration of fetal liver cells to the fetal thymus. J Immunol 163:3211–3216

  25. Kawamoto K, Ohmura K, Katsura Y (1997) Direct evidence for the commitment of hematopoietic stem cells to T, B, and myeloid lineages in murine fetal liver. Int Immunol 9:1011–1019

  26. Kuhnlein P, Vicente A, Varas A, Hunig T, Zapata A (1995) Gamma/delta T cells in fetal, neonatal, and adult rat lymphoid organs. Dev Immunol 4:181–188

  27. Kutleša S, Siler U, Speiser A, Wessels JT, Virtanen I, Rousselle L, Sorokin M, Müller CA, Klein G (2002a) Developmentally regulated interactions of human thymocytes with different laminin isoforms. Immunology 105:407–418

  28. Kutleša S, Wessels JT, Speiser A, Steiert I, Müller CA, Klein G (2002b) E-cadherin-mediated interactions of thymic epithelial cells with CD103+ thymocytes lead to enhanced thymocyte cell proliferation. J Cell Sci 115:4505–4515

  29. Manley NR, Blackburn CC (2003) A developmental look at thymus organogenesis: where do the non-hematopoietic cells in the thymus come from? Curr Opin Immunol 15:225–232

  30. Manz MG, Traver D, Miyamoto T, Weissman IL, Akashi K (2001) Dendritic cell potentials of early lymphoid and myeloid progenitors. Blood 97:3333–3341

  31. Muller KM, Luedecker CJ, Udey MC, Farr AG (1997) Involvement of E-cadherin in thymus organogenesis and thymocyte maturation. Immunity 6:257–264

  32. Nieto M, Gomez P, Sanchez-Mateos P, Fernandez E, Mazauela M, Sacedon R, Varas A, Gonzalez-Amaro R, Zapata AG, Toribo ML, Sanchez-Madrid F (1996) Expression of functionally active α4β1 integrin by thymic epithelial cells. Clin Exp Immunol 106:170–178

  33. Norment AM, Bevan MJ (2000) Role of chemokines in thymocyte development. Semin Immunol 12:445–455

  34. Owen JJ, McLoughlin DE, Suniara RK, Jenkinson EJ (2000) The role of mesenchyme in thymus development. Curr Top Microbiol Immunol 251:133–137

  35. Rees EP van, Dijkstra CD, Sminia T (1990) Ontogeny of the rat immune system: an immunohistochemical approach. Dev Comp Immunol 14:9–18

  36. Revest J-M, Suniara RK, Kerr K, Owen JJT, Dickson C (2001) Development of the thymus requires signaling through the fibroblast growth factor receptor R2-IIIb. J Immunol 167:1954–1961

  37. Shinohara T, Honjo T (1997) Studies in vitro on the mechanism of the epithelial/mesenchyme interaction in the early fetal thymus. Eur J Immunol 27:522–529

  38. Shores EW, Ewijk W van, Singer A (1994) Maturation of medullary thymic epithelium requires thymocytes expressing fully assembled CD3-TCR complexes. Int Immunol 6:1393–1402

  39. Suniara RK, Jenkinson EJ, Owen JJT (2000) An essential role for thymic mesenchyme in early T cell development. J Exp Med 191:1051–1056

  40. Ushiki T, Iwanaga T, Masuda T, Takahashi Y, Fujita T (1984) Distribution and ultrastructure of S-100-immunoreactive cells in the human thymus. Cell Tissue Res 235:509–514

  41. Vicente A, Varas L, Alonso L, Gómez de Moral M, Zapata AG (1994) Ontogeny of rat thymic dendritic cells. Immunology 82:75–81

  42. Vicente A, Varas A, Acedon RS, Jimenez E, Munoz JJ, Zapata AG (1998a) Appearance and maturation of T-cell subsets during rat thymus ontogeny. Dev Immunol 5:319–331

  43. Vicente A, Varas A, Sacedon R, Zapata AG (1998b) Histogenesis of the epithelial component of rat thymus: an ultrastructural and immunohistological analysis. Anat Rec 244:506–519

  44. Wilkinson B, Owen JJT, Jenkinson EJ (1999) Factors regulating stem cell recruitment to the fetal thymus. J Immunol 162:3873–3881

  45. Zaitseva M, Kawamura T, Loomis R, Goldsten H, Blauvelt A, Golding H (2002) Stromal-derived factor 1 expression in the human thymus. J Immunol 168:2609–2617

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Acknowledgements

Our thanks are due to Dr. J. Jaroszewski for useful comments.

Author information

Correspondence to Renata Brelinska.

Additional information

This study was supported by UMS grant 501-2-0003404.

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Brelinska, R., Malinska, A. Homing of hemopoietic precursor cells to the fetal rat thymus: intercellular contact-controlled cell migration and development of the thymic microenvironment. Cell Tissue Res 322, 393–405 (2005). https://doi.org/10.1007/s00441-005-1079-7

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Keywords

  • Thymus
  • Organogenesis
  • Ultrastructure
  • Fibroblast
  • Dendritic cell
  • Epithelial cell
  • Rat (Wistar)