Immunologic Research

, Volume 6, Issue 4, pp 238–249 | Cite as

Molecular biological definition of the prothymocyte: Problems of commitment and lineage promiscuity

  • Allen E. Silverstone
  • Martin A. R. Yuille
Competition The Prothymocyte Symposium


Doubly Nega Bluestone BUdR Doubly Nega Thymocyte Fetal Thymocyte 
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  1. 1.
    Silverstone, A.E.: The prothymocyte revisited. Surv. immunol. Res.4: 1–5 (1985).PubMedGoogle Scholar
  2. 2.
    Silverstone, A.E.: The prothymocyte and commitment of T-cell differentiation, in Cruse, Lewis, The year in immunology 1984–85, pp. 80–85 (Karger, Basel 1985).Google Scholar
  3. 3.
    Boyse, E.A.: The prothymocyte: cellular and molecular biology. Surv. immunol. Res.4 6–10 (1985).PubMedGoogle Scholar
  4. 4.
    Silverstone, A.E.; Cantor, H.; Goldstein, G.; Baltimore, D.: Terminal deoxynucleotidyl transferase is found in prothymocytes. J. exp. Med144: 543–549 (1976).PubMedCrossRefGoogle Scholar
  5. 5.
    Basch, R.S.; Kadish, J.L.; Goldstein, G.: Hematopoietic thymocyte precursors, IV. Enrichment of the precursors and evidence for heterogeneity. J. exp. Med.147: 1843–1848 (1978).PubMedCrossRefGoogle Scholar
  6. 6.
    Koning, F.; Stingl, G.; Yokoyama, W.M.; Yamada, H.; Maloy, W.L.; Tschachler, E.; Shevach, E.M.; Coligan, J.E.: Identification of a T3 associated γ/δ T cell receptor on Thy-1+dendritic epidermal cell lines. Science236: 834–837 (1987).PubMedCrossRefGoogle Scholar
  7. 7.
    Maleckar, J.R.; Sherman, L.A.: The composition of the T cell receptor repertoire in nude mice. J. Immun.138: 3873–3876 (1987).PubMedGoogle Scholar
  8. 8.
    Greaves, M.F.; Chan, L.C.; Furley, A.J.W.; Watt, S.M.; Molgaard, H.V.: Lineage promiscuity in hemopoietic differentiation and leukemia. Blood67: 1–11 (1986).PubMedGoogle Scholar
  9. 9.
    McCulloch, E.A.: Lineage infidelity or lineage promiscuity? Leukemia1: 235 (1987).PubMedGoogle Scholar
  10. 10.
    Fowlkes, B.J.: Intrathymic differentiation: introductory remarks on problems and approaches. Surv. immunol. Res.4: 81–86 (1985).PubMedGoogle Scholar
  11. 11.
    Weissman, I.L.: Thymus cell migration. J. exp. Med.126: 291–318 (1967).PubMedCrossRefGoogle Scholar
  12. 12.
    Scollay, R.; Smith, J.; Stauffer, V.: Dynamics of early T cells: prothymocyte migration and proliferation in the adult mouse thymus. Immunol. Rev.91: 129–157 (1986).PubMedCrossRefGoogle Scholar
  13. 13.
    Adkins, B.; Mueller, C.; Okada, C.Y.; Reichert, R.A.; Weissman, I.L.; Spangrude, G.J.: Early events in T-cell maturation. Annu. Rev. Immunol.5: 325–365 (1987).PubMedCrossRefGoogle Scholar
  14. 14.
    Owen, J.J.T.; Jenkinson, E.J.: Embryology of the lymphoid system. Prog. Allergy, vol. 29, pp. 1–34 (Karger, Basel 1981).Google Scholar
  15. 15.
    Williams, G.T.; Kingston, R.; Owen, M.J.; Jenkinson, E.J.; Owen, J.J.T.: A single micromanipulated stem cell gives rise to multiple T-cell receptor gene rearrangements in the thymus in vitro. Nature324: 63–64 (1986).PubMedCrossRefGoogle Scholar
  16. 16.
    Champion, S.; Imhof, B.A.; Savagner, P.; Thiery, J.P.: The embryonic thymus produces chemotactic peptides involved in the homing of hemopoietic precursors. Cell44: 781–790 (1986).PubMedCrossRefGoogle Scholar
  17. 17.
    Mossalayi, D; Ahmad, M.; Tanzer, J.; Janossy, G.; LaForest, P.G. de: Studies on human prothymocytes by means of an agar T-cell colony assay. Exp. Hematol.14: 351–357 (1986).PubMedGoogle Scholar
  18. 18.
    Sideras, P.; Palacios, R.: Bone marrow pro-T and pro-B lymphocyte clones express functional receptors for interleukin (IL)3 and IL4/BSF-1 and non functional receptors for IL2. Eur. J. Immunol17: 217–221 (1987).PubMedCrossRefGoogle Scholar
  19. 19.
    Oettgen, H.C.; Terhorst, C.: A review of the structure and function of the T-cell receptor-T-3 complex. CRC crit. Rev. Biochem. (in press).Google Scholar
  20. 20.
    Rothenberg, E.V.; Lugo, J.P.: Differentiation and cell division in the mammalian thymus. Devl Biol.112: 1–17 (1985).CrossRefGoogle Scholar
  21. 21.
    Dongen, J.J.M. van; Quertermous, T.; Bartram, C.R.; Gold, D.P.; Wolvers-Tettero, I.L.M.; Comans-Bitter, W.M.; Hooijkaas, H.; Adriaansen, H.J.; Klein, A. de; Raghavachar, A.; Ganser, A.; Duby, A.D.; Seidman, J.G.; Elsen, P. van den; Terhorst, C.: T-cell receptor-CD3 complex during early T cell differentiation. J. Immun.138: 1260–1269 (1987).PubMedGoogle Scholar
  22. 22.
    Vasmel, W.L.E.; Radaszkiewicz, T.; Miltenburg, A.M.; Zijlstra, M.; and Melief, C.J.M.: Refinement and precision in the classification of murine lymphomas by genotyping with immunoglobulin and T-cell receptor probes. Leukemia1: 155–162 (1987).PubMedGoogle Scholar
  23. 23.
    Furley, A.J.; Mizutani, S.; Weilbacher K.; Dhaliwal, H.S.; Ford, A.M.; Chan, L.C.; Molgaard, H.V.; Toyonaga, B.; Mak, T.; Elsen, P. van den; Gold, D.; Terhorst, C.; Greaves, M.F.: Developmentally regulated rearrangement and expression of genes encoding the T cell receptor-T3 complex. Cell46: 75–87 (1986).PubMedCrossRefGoogle Scholar
  24. 24.
    Greenberg, J.M.; Quertermous, T.; Seidman, J.G.; Kersey, J.H.: Human T cell γ chain gene rearrangements in acute lymphoid and nonlymphoid leukemia: comparison with the T cell receptor β chain gene. J. Immun.137: 2043–2049 (1986).PubMedGoogle Scholar
  25. 25.
    Greenberg, J.M.; Kersey, J.H.: Terminal deoxynucleotidyl transferase expression can precede T cell receptor β chain and γ chain rearrangement in T cell acute lymphoblastic leukemia. Blood69: 356–360 (1987)PubMedGoogle Scholar
  26. 26.
    Lefranc, M.-P.; Forster, A.; Rabbitts, T.H.: Organization and rearrangement of human T-cell rearranging γ genes. J. cell. Biochem., suppl.11D: 214 (1987)Google Scholar
  27. 27.
    Cook, W.D.; Balaton, A.M.: T-cell receptor and immunoglobulin genes are rearranged together in abelson virus-transformed pre-B and pre-T cells. Mol. cell. Biol.7: 266–272 (1987).PubMedGoogle Scholar
  28. 28.
    Cheng, G.Y.; Minden, M.D.; Toyonaga, B.; Mak, T.W.; McCulloch, E.A.: T-cell receptor and immunoglobulin gene rearrangements in acute myeloblastic leukemia. J. exp. Med.163: 414–424 (1986).PubMedCrossRefGoogle Scholar
  29. 29.
    Foa, R.; Casorati, G.; Giobellino, C.; Basso, G.; Schiro, R.; Giovanni, P.; Lauria, F.; LeFranc, M.-P.; Rabbitts, T.H.; Migone, N.: Rearrangements of immunoglobulin and T cell receptor β and γ genes are associated with terminal deoxynucleotidyl transferase expression in acute myeloid leukemia. J. exp. Med.165: 879–890 (1987).PubMedCrossRefGoogle Scholar
  30. 30.
    Lew, A.M.; Pardoll, D.M.; Maloy, W.L.; Fowlkes, B.J.; Kruisbeek, A.; Cheng, S.-F.; Germain, R.N.; Bluestone, J.A.; Schwartz, R.H.; Coligen, J.E.: characterization of T-cell receptor gamma chain expression in a subset of murine thymocytes. Science234: 1401–1405 (1986).PubMedCrossRefGoogle Scholar
  31. 31.
    Jones, B.; Mjolsness, S.; Janeway, C., Jr.; Hayday, A.C.: Transcripts of functionally rearranged gamma genes in primary T cells of adult immunocompetent mice. Nature323: 635–638 (1986).PubMedCrossRefGoogle Scholar
  32. 32.
    Sacchi, N.; Fiorini, G.; Plevani, P.; Badaracco, G.; Brevario, D.; Ginelli, E.: Acquisition of deoxyguanosine resistance by TPA-induced T lymphoid lines. J. Immun.130: 1622–1626 (1983).PubMedGoogle Scholar
  33. 33.
    Silverstone, A.E.; Beland, J.L.: TPA induces growth factor dependence in a pre-T cell line and loss of terminal transferase RNA. J. cell. Biochem., suppl.11D: 235 (1987).Google Scholar
  34. 34.
    Campana, D.; Thompson, J.S.; Amlot, P.; Brown, S.; Janossy, G.: The cytoplasmic expression of CD3 antigens in normal and malignant cells of the T lymphoid lineage. J. Immun.138: 648–655 (1987).PubMedGoogle Scholar
  35. 35.
    Lesley, J.; Trotter, J.; Hyman, R.: The Pgp-1 antigen is expressed on early fetal thymocytes. Immunogenetics22: 149–157 (1985).PubMedCrossRefGoogle Scholar
  36. 36.
    Lynch, F.; Chaudhri, G.; Allan, J.E.; Doherty, P.C.; Ceredig, R.: Expression of Pgp-1 (or Ly 24) by subpopulations of mouse thymocytes and activated peripheral T lymphocytes. Eur. J. Immunol.17: 137–140 (1987).PubMedCrossRefGoogle Scholar
  37. 37.
    Nakanishi, N.; Maeda, K.; Ito, K.; Heller, M.; Tonegawa, S.: T γ protein is expressed on murine fetal thymocytes as a disulphide-linked heterodimer. Nature325: 720–723 (1987).PubMedCrossRefGoogle Scholar
  38. 38.
    Pardoll, D.M.; Fowlkes, B.J.; Bluestone, J.A.; Kruisbeek, A.; Maloy, W.L.; Coligen, J.E.; Schwartz, R.H.: Differential expression of two distinct T-cell receptors during thymocyte development. Nature326: 79–81 (1987).PubMedCrossRefGoogle Scholar
  39. 39.
    Okazaki, K.; Davis, D.D.; Sakano, H.: T cell receptor β gene sequences in the circular DNA of thymocyte nuclei: direct evidence for intramolecular DNA deletion in V-D-J joining. Cell49: 477–485 (1987).PubMedCrossRefGoogle Scholar
  40. 40.
    Alt, F.W.; Yancopoulos, G.D.: Circular T-cell receptor gene recombination products. Nature327: 189–190 (1987).PubMedCrossRefGoogle Scholar
  41. 41.
    Kincade, P.W.; Lee, G.; Watanabe, T.; Sun, L.; Scheid, M.P.: Antigens displayed on murine B lymphocyte precursors. J. Immun.127: P2262.Google Scholar
  42. 42.
    Park, Y.-H.; Osmond, D.G.: Phenotype and proliferation of early B lymphocyte precursor cells in mouse bone marrow. J. exp. Med.165: 444–458 (1987).PubMedCrossRefGoogle Scholar
  43. 43.
    Bluestone, J.A.; Pardoll, D.; Sharrow, S.O.; Fowlkes, B.J.: Characterization of murine thymocytes with CD3 associated T-cell receptor structures. Nature326: 82–84 (1987).PubMedCrossRefGoogle Scholar
  44. 44.
    Lanier, L.L.; Weiss, A.: Presence of Ti(WT31) negative T lymphocytes in normal blood and thymus. Nature324: 268–270 (1986).PubMedCrossRefGoogle Scholar
  45. 45.
    Borst, J.; Gried, R.J. de; Oostveen, J.W. van; Ang, S-L.; Melief, C.J.; Seidman, J.G.; Bolhuis, R.L.H.: A T-cell receptor γ/CD3 complex found on cloned functional lymphocytes. Nature325: 683–688 (1987).PubMedCrossRefGoogle Scholar
  46. 46.
    Reinherz, E.L.: T-cell receptors: who needs more? Nature325: 660–663 (1987).PubMedCrossRefGoogle Scholar
  47. 47.
    Toribio, M.L.; Martinez-A., C.; Marcos, M.A.R.; Marquez, C.; Cabrer, E.; Hera, A. de la: A role for T3+4-6-8- transitional thymocytes in the differentiation of mature and functional T cells from human prothymocytes. Proc. natn. Acad. Sci. USA83: 6985–6988 (1986).CrossRefGoogle Scholar
  48. 48.
    Tutt, M.M.; Schuler, W.; Kuziel, W.A.; Tucker, P.W.; Bennett, M.; Bosma, M.J.; Kumar, V.: T cell receptor genes do not rearrange or express functional transcripts in natural killer cells ofscid mice. J. Immun.138: 2338–2344 (1987).PubMedGoogle Scholar
  49. 49.
    Stutman, O.: Postthymic T-cell development. Immunol. Rev.91: 159–194 (1986).PubMedCrossRefGoogle Scholar
  50. 50.
    Goldschneider, I.; Komschlies, K.L.; Greiner, D.L.: Studies of thymocytopoiesis in rats and mice. I. Kinetics of appearance of thymocytes using a direct intrathymic adoptive transfer assay for thymocyte precursors. J. exp. Med.163: 1–17 (1986).PubMedCrossRefGoogle Scholar
  51. 51.
    Greiner, D.L.; Goldschneider, I.; Komschlies, K.L.; Medlock, E.S.; Bollum, F.J.; Schultz, L.: Defective lymphopoiesis in bone marrow of motheaten (me/me) and viable motheaten (me v/me v) mutant mice. I. Analysis of development of prothymocytes, early B lineage cells, and terminal deoxynucleotidyl transferase-positive cells. J. exp. Med.164: 1129–1144 (1986).PubMedCrossRefGoogle Scholar
  52. 52.
    Medlock, E.S.; Goldschneider, I.; Greiner, D.L.; Schultz, L.: Defective lymphopoiesis in the bone marrow of motheaten (me/me) and viable motheaten (me v/me v) mutant mice. II. Description of a microenvironmental defect for the generation of terminal deoxynucleotidyltransferase-positive bone marrow cells in vitro. J. Immun.138: 3590–3597 (1987).PubMedGoogle Scholar
  53. 53.
    Silverstone, A.E.; Rosenberg, N.; Baltimore, D.; Sato, V.L.; Scheid, M.P.; Boyse, E.A.: Correlating terminal deoxynucleotidyl transferase and cell-surface markers in the pathway of lymphocyte ontogeny: in Clarkson, Marks, Till, Differentiation of normal and neoplastic hematopoietic cells. Cold Spring Harb. Conf. Immunol. Cell Proliferation, vol. 5, pp. 433–453 (Cold Spring Harbor Laboratory, Cold Spring Harbor 1978).Google Scholar
  54. 54.
    Penit, C.; Jotereau, F.; Gelabert, M.J.: Relationships between terminal transferase expression, stem cell colonization, and thymic maturation in the avian embryo: studies in thymic chimeras resulting from homospecific and heterospecific grafts. J. Immun.134: 2149–2154 (1985).PubMedGoogle Scholar
  55. 55.
    Goodwin, L.O.; Rocha, A.J.D.; Basch, R.S.: Isolation of cell lines possessing functional and serological properties resembling those of prothymocytes. Nature323: 165–169 (1986).CrossRefGoogle Scholar
  56. 56.
    Alt, F.W.; Blackwell, T.K.; DePinho, R.A.; Reth, M.G.; Yancopoulos, G.D.: Regulation of genome rearrangement events during lymphocyte differentiation. Immunol. Rev.89: 5–30 (1986).PubMedCrossRefGoogle Scholar
  57. 57.
    Stavnezer-Nordgren, J.; Sirlin, S.: Specificity of immunoglobulin heavy chain switch correlates with activity of germline heavy chain genes prior to switching. EMBO J.5: 95–102 (1986).PubMedGoogle Scholar
  58. 58.
    Sen, R.; and Baltimore, D.: Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell46: 705–716 (1986).PubMedCrossRefGoogle Scholar
  59. 59.
    Maniatis, T.; Goodbourn, S.; Fischer, J.A.: Regulation of inducible and tissue-specific gene expression. Science236: 1237–1245 (1987).PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1987

Authors and Affiliations

  • Allen E. Silverstone
    • 1
  • Martin A. R. Yuille
    • 1
  1. 1.Department of Microbiology and ImmunologySUNY Health Science Center at SyracuseSyracuse(USA)

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