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. 1996 Nov 1;184(5):1901–1908. doi: 10.1084/jem.184.5.1901

Isolation of the most immature population of murine fetal thymocytes that includes progenitors capable of generating T, B, and myeloid cells

PMCID: PMC2192886  PMID: 8920877

Abstract

Thymus cells of murine fetuses at day 12 of gestation are exclusively of the CD3-CD4-CD8-CD44+CD25- phenotype, which is known as a hallmark of the most immature subset of thymus cells. In the present study, we show that day 12 fetal thymus (FT) cells express Fc gamma RII/ III (FcR) at a broad range of levels on their surface. The FcR+ FT cells seem to represent T lineage cells, because a large majority of them express the T lineage specific transcription factors TCF-1 and GATA-3 as well as CD3 epsilon in the cytoplasm. Also shown is that the FcR- population contains progenitors capable of developing into not only T cells but also B and myeloid cells, whereas FcR+ progenitors are mostly committed to the T lineage. These findings indicate that thymic T lineage cells express FcR on their surface at the earliest stage of differentiation, and thus FcR is a useful marker in isolating the most immature population of murine FT cells.

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Selected References

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  1. Amagai T., Itoi M., Kondo Y. Limited development capacity of the earliest embryonic murine thymus. Eur J Immunol. 1995 Mar;25(3):757–762. doi: 10.1002/eji.1830250320. [DOI] [PubMed] [Google Scholar]
  2. Carlsson L., Candéias S., Staerz U., Keller G. Expression of Fc gamma RIII defines distinct subpopulations of fetal liver B cell and myeloid precursors. Eur J Immunol. 1995 Aug;25(8):2308–2317. doi: 10.1002/eji.1830250829. [DOI] [PubMed] [Google Scholar]
  3. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  4. Dou Y. M., Watanabe Y., Aiba Y., Wada K., Katsura Y. A novel culture system for induction of T cell development: modification of fetal thymus organ culture. Thymus. 1994;23(3-4):195–207. [PubMed] [Google Scholar]
  5. Ferrick D. A., Schrenzel M. D., Mulvania T., Hsieh B., Ferlin W. G., Lepper H. Differential production of interferon-gamma and interleukin-4 in response to Th1- and Th2-stimulating pathogens by gamma delta T cells in vivo. Nature. 1995 Jan 19;373(6511):255–257. doi: 10.1038/373255a0. [DOI] [PubMed] [Google Scholar]
  6. Godfrey D. I., Kennedy J., Suda T., Zlotnik A. A developmental pathway involving four phenotypically and functionally distinct subsets of CD3-CD4-CD8- triple-negative adult mouse thymocytes defined by CD44 and CD25 expression. J Immunol. 1993 May 15;150(10):4244–4252. [PubMed] [Google Scholar]
  7. Godfrey D. I., Zlotnik A. Control points in early T-cell development. Immunol Today. 1993 Nov;14(11):547–553. doi: 10.1016/0167-5699(93)90186-O. [DOI] [PubMed] [Google Scholar]
  8. Hattori N., Kawamoto H., Fujimoto S., Kuno K., Katsura Y. Involvement of transcription factors TCF-1 and GATA-3 in the initiation of the earliest step of T cell development in the thymus. J Exp Med. 1996 Sep 1;184(3):1137–1147. doi: 10.1084/jem.184.3.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ikuta K., Uchida N., Friedman J., Weissman I. L. Lymphocyte development from stem cells. Annu Rev Immunol. 1992;10:759–783. doi: 10.1146/annurev.iy.10.040192.003551. [DOI] [PubMed] [Google Scholar]
  10. Kurtzberg J., Denning S. M., Nycum L. M., Singer K. H., Haynes B. F. Immature human thymocytes can be driven to differentiate into nonlymphoid lineages by cytokines from thymic epithelial cells. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7575–7579. doi: 10.1073/pnas.86.19.7575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Marth J. D., Peet R., Krebs E. G., Perlmutter R. M. A lymphocyte-specific protein-tyrosine kinase gene is rearranged and overexpressed in the murine T cell lymphoma LSTRA. Cell. 1985 Dec;43(2 Pt 1):393–404. doi: 10.1016/0092-8674(85)90169-2. [DOI] [PubMed] [Google Scholar]
  12. Matsuzaki Y., Gyotoku J., Ogawa M., Nishikawa S., Katsura Y., Gachelin G., Nakauchi H. Characterization of c-kit positive intrathymic stem cells that are restricted to lymphoid differentiation. J Exp Med. 1993 Oct 1;178(4):1283–1292. doi: 10.1084/jem.178.4.1283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nikolić-Zugić J. Phenotypic and functional stages in the intrathymic development of alpha beta T cells. Immunol Today. 1991 Feb;12(2):65–70. doi: 10.1016/0167-5699(91)90160-u. [DOI] [PubMed] [Google Scholar]
  14. Nishikawa S., Ogawa M., Nishikawa S., Kunisada T., Kodama H. B lymphopoiesis on stromal cell clone: stromal cell clones acting on different stages of B cell differentiation. Eur J Immunol. 1988 Nov;18(11):1767–1771. doi: 10.1002/eji.1830181117. [DOI] [PubMed] [Google Scholar]
  15. Ogawa M., Matsuzaki Y., Nishikawa S., Hayashi S., Kunisada T., Sudo T., Kina T., Nakauchi H., Nishikawa S. Expression and function of c-kit in hemopoietic progenitor cells. J Exp Med. 1991 Jul 1;174(1):63–71. doi: 10.1084/jem.174.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Papiernik M., Lepault F., Pontoux C. Synergistic effect of colony-stimulating factors and IL-2 on prothymocyte proliferation linked to the maturation of macrophage/dendritic cells within L3T4-Lyt-2-Ia-Mac- cells. J Immunol. 1988 Mar 1;140(5):1431–1434. [PubMed] [Google Scholar]
  17. Péault B., Khazaal I., Weissman I. L. In vitro development of B cells and macrophages from early mouse fetal thymocytes. Eur J Immunol. 1994 Mar;24(3):781–784. doi: 10.1002/eji.1830240345. [DOI] [PubMed] [Google Scholar]
  18. Rodewald H. R., Kretzschmar K., Takeda S., Hohl C., Dessing M. Identification of pro-thymocytes in murine fetal blood: T lineage commitment can precede thymus colonization. EMBO J. 1994 Sep 15;13(18):4229–4240. doi: 10.1002/j.1460-2075.1994.tb06743.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rodewald H. R., Moingeon P., Lucich J. L., Dosiou C., Lopez P., Reinherz E. L. A population of early fetal thymocytes expressing Fc gamma RII/III contains precursors of T lymphocytes and natural killer cells. Cell. 1992 Apr 3;69(1):139–150. doi: 10.1016/0092-8674(92)90125-v. [DOI] [PubMed] [Google Scholar]
  20. Rodewald H. R. Pathways from hematopoietic stem cells to thymocytes. Curr Opin Immunol. 1995 Apr;7(2):176–187. doi: 10.1016/0952-7915(95)80002-6. [DOI] [PubMed] [Google Scholar]
  21. Saint-Ruf C., Ungewiss K., Groettrup M., Bruno L., Fehling H. J., von Boehmer H. Analysis and expression of a cloned pre-T cell receptor gene. Science. 1994 Nov 18;266(5188):1208–1212. doi: 10.1126/science.7973703. [DOI] [PubMed] [Google Scholar]
  22. Sakaguchi N., Kashiwamura S., Kimoto M., Thalmann P., Melchers F. B lymphocyte lineage-restricted expression of mb-1, a gene with CD3-like structural properties. EMBO J. 1988 Nov;7(11):3457–3464. doi: 10.1002/j.1460-2075.1988.tb03220.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sandor M., Galon J., Takacs L., Tatsumi Y., Mueller A. L., Sautes C., Lynch R. G. An alternative Fc gamma-receptor ligand: potential role in T-cell development. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12857–12861. doi: 10.1073/pnas.91.26.12857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sandor M., Lynch R. G. Lymphocyte Fc receptors: the special case of T cells. Immunol Today. 1993 May;14(5):227–231. doi: 10.1016/0167-5699(93)90168-K. [DOI] [PubMed] [Google Scholar]
  25. Sherr C. J., Rettenmier C. W., Sacca R., Roussel M. F., Look A. T., Stanley E. R. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell. 1985 Jul;41(3):665–676. doi: 10.1016/s0092-8674(85)80047-7. [DOI] [PubMed] [Google Scholar]
  26. Takai T., Li M., Sylvestre D., Clynes R., Ravetch J. V. FcR gamma chain deletion results in pleiotrophic effector cell defects. Cell. 1994 Feb 11;76(3):519–529. doi: 10.1016/0092-8674(94)90115-5. [DOI] [PubMed] [Google Scholar]
  27. Unkeless J. C. Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors. J Exp Med. 1979 Sep 19;150(3):580–596. doi: 10.1084/jem.150.3.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wada K., Kina T., Kawamoto H., Kondo M., Katsura Y. Requirement of cell interactions through adhesion molecules in the early phase of T cell development. Cell Immunol. 1996 May 25;170(1):11–19. doi: 10.1006/cimm.1996.0128. [DOI] [PubMed] [Google Scholar]
  29. Watanabe Y., Gyotoku J., Katsura Y. Analysis of the development of T cells by transferring precursors into cultured fetal thymus with a microinjector. Thymus. 1989;13(1-2):57–71. [PubMed] [Google Scholar]
  30. Watanabe Y., Katsura Y. Development of T cell receptor alpha beta-bearing T cells in the submersion organ culture of murine fetal thymus at high oxygen concentration. Eur J Immunol. 1993 Jan;23(1):200–205. doi: 10.1002/eji.1830230131. [DOI] [PubMed] [Google Scholar]
  31. Wilson A., MacDonald H. R. Expression of genes encoding the pre-TCR and CD3 complex during thymus development. Int Immunol. 1995 Oct;7(10):1659–1664. doi: 10.1093/intimm/7.10.1659. [DOI] [PubMed] [Google Scholar]
  32. Wittwer C. T., Fillmore G. C., Garling D. J. Minimizing the time required for DNA amplification by efficient heat transfer to small samples. Anal Biochem. 1990 May 1;186(2):328–331. doi: 10.1016/0003-2697(90)90090-v. [DOI] [PubMed] [Google Scholar]
  33. Wittwer C. T., Fillmore G. C., Hillyard D. R. Automated polymerase chain reaction in capillary tubes with hot air. Nucleic Acids Res. 1989 Jun 12;17(11):4353–4357. doi: 10.1093/nar/17.11.4353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wu L., Antica M., Johnson G. R., Scollay R., Shortman K. Developmental potential of the earliest precursor cells from the adult mouse thymus. J Exp Med. 1991 Dec 1;174(6):1617–1627. doi: 10.1084/jem.174.6.1617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. de Weers M., Verschuren M. C., Kraakman M. E., Mensink R. G., Schuurman R. K., van Dongen J. J., Hendriks R. W. The Bruton's tyrosine kinase gene is expressed throughout B cell differentiation, from early precursor B cell stages preceding immunoglobulin gene rearrangement up to mature B cell stages. Eur J Immunol. 1993 Dec;23(12):3109–3114. doi: 10.1002/eji.1830231210. [DOI] [PubMed] [Google Scholar]

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