Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1994 Aug 1;180(2):569–576. doi: 10.1084/jem.180.2.569

Identification of a common T/natural killer cell progenitor in human fetal thymus

PMCID: PMC2191594  PMID: 7519241

Abstract

The phenotypic similarities between natural killer (NK) and T cells have led to the hypothesis that these distinctive lymphocyte subsets may be developmentally related and thus may share a common progenitor (Lanier, L. L., H. Spits, and J. H. Phillips, 1992. Immunol. Today. 13:392; Rodewald, H.-R., P. Moingeon, J. L. Lurich, C. Dosiou, P. Lopez, and E. L. Reinherz. 1992. Cell. 69:139). In this report, we have investigated the potential of human CD34+ triple negative thymocytes ([TN] CD3-, CD4-, CD8-) to generate both T cells and NK cells in murine fetal thymic organ cultures (mFTOC) and in vitro clonogenic assays. CD34+ TN thymocytes, the majority of which express prominent cytoplasmic CD3 epsilon (cytoCD3 epsilon) protein, can be divided into high (CD34Bright) and low (CD34Dim) surface expressing populations. CD34Bright TN thymocytes were capable of differentiating into T and NK cells when transferred into mFTOC, and demonstrated high NK cell clonogenic capabilities when cultured in interleukin (IL)-2, IL-7, and stem cell factor (SCF). Likewise, CD34Bright TN thymocyte clones after 5 d in culture were capable of generating NK and T cells when transferred into mFTOC but demonstrated clonogenic NK cell differentiation capabilities when maintained in culture with IL-2. CD34Dim TN thymocytes, however, possessed only T cell differentiation capabilities in mFTOC but were not expandable in clonogenic conditions containing IL-2, IL-7, and SCF. No significant differentiation of other cell lineage was detected in either mFTOC or in clonogenic assays from CD34+ TN thymocytes. These results represent the first definitive evidence of a common T/NK cell progenitor in the human fetal thymus and delineate the point in thymocyte differentiation where T and NK cells diverge.

Full Text

The Full Text of this article is available as a PDF (828.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andrews R. G., Takahashi M., Segal G. M., Powell J. S., Bernstein I. D., Singer J. W. The L4F3 antigen is expressed by unipotent and multipotent colony-forming cells but not by their precursors. Blood. 1986 Nov;68(5):1030–1035. [PubMed] [Google Scholar]
  2. Baum C. M., Weissman I. L., Tsukamoto A. S., Buckle A. M., Peault B. Isolation of a candidate human hematopoietic stem-cell population. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2804–2808. doi: 10.1073/pnas.89.7.2804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bárcena A., Muench M. O., Galy A. H., Cupp J., Roncarolo M. G., Phillips J. H., Spits H. Phenotypic and functional analysis of T-cell precursors in the human fetal liver and thymus: CD7 expression in the early stages of T- and myeloid-cell development. Blood. 1993 Dec 1;82(11):3401–3414. [PubMed] [Google Scholar]
  4. Caux C., Dezutter-Dambuyant C., Schmitt D., Banchereau J. GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature. 1992 Nov 19;360(6401):258–261. doi: 10.1038/360258a0. [DOI] [PubMed] [Google Scholar]
  5. Fisher A. G., Larsson L., Goff L. K., Restall D. E., Happerfield L., Merkenschlager M. Human thymocyte development in mouse organ cultures. Int Immunol. 1990;2(6):571–578. doi: 10.1093/intimm/2.6.571. [DOI] [PubMed] [Google Scholar]
  6. Galy A., Verma S., Bárcena A., Spits H. Precursors of CD3+CD4+CD8+ cells in the human thymus are defined by expression of CD34. Delineation of early events in human thymic development. J Exp Med. 1993 Aug 1;178(2):391–401. doi: 10.1084/jem.178.2.391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Griffin J. D., Ritz J., Nadler L. M., Schlossman S. F. Expression of myeloid differentiation antigens on normal and malignant myeloid cells. J Clin Invest. 1981 Oct;68(4):932–941. doi: 10.1172/JCI110348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hall C., Berkhout B., Alarcon B., Sancho J., Wileman T., Terhorst C. Requirements for cell surface expression of the human TCR/CD3 complex in non-T cells. Int Immunol. 1991 Apr;3(4):359–368. doi: 10.1093/intimm/3.4.359. [DOI] [PubMed] [Google Scholar]
  9. Hori T., Cupp J., Wrighton N., Lee F., Spits H. Identification of a novel human thymocyte subset with a phenotype of CD3- CD4+ CD8 alpha + beta-1. Possible progeny of the CD3- CD4- CD8- subset. J Immunol. 1991 Jun 15;146(12):4078–4084. [PubMed] [Google Scholar]
  10. Huang S., Terstappen L. W. Formation of haematopoietic microenvironment and haematopoietic stem cells from single human bone marrow stem cells. Nature. 1992 Dec 24;360(6406):745–749. doi: 10.1038/360745a0. [DOI] [PubMed] [Google Scholar]
  11. Kraft D. L., Weissman I. L., Waller E. K. Differentiation of CD3-4-8- human fetal thymocytes in vivo: characterization of a CD3-4+8- intermediate. J Exp Med. 1993 Jul 1;178(1):265–277. doi: 10.1084/jem.178.1.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Lanier L. L., Chang C., Spits H., Phillips J. H. Expression of cytoplasmic CD3 epsilon proteins in activated human adult natural killer (NK) cells and CD3 gamma, delta, epsilon complexes in fetal NK cells. Implications for the relationship of NK and T lymphocytes. J Immunol. 1992 Sep 15;149(6):1876–1880. [PubMed] [Google Scholar]
  14. Lanier L. L., Le A. M., Phillips J. H., Warner N. L., Babcock G. F. Subpopulations of human natural killer cells defined by expression of the Leu-7 (HNK-1) and Leu-11 (NK-15) antigens. J Immunol. 1983 Oct;131(4):1789–1796. [PubMed] [Google Scholar]
  15. Lanier L. L., Spits H., Phillips J. H. The developmental relationship between NK cells and T cells. Immunol Today. 1992 Oct;13(10):392–395. doi: 10.1016/0167-5699(92)90087-N. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Nagler A., Lanier L. L., Cwirla S., Phillips J. H. Comparative studies of human FcRIII-positive and negative natural killer cells. J Immunol. 1989 Nov 15;143(10):3183–3191. [PubMed] [Google Scholar]
  18. Phillips J. H., Hori T., Nagler A., Bhat N., Spits H., Lanier L. L. Ontogeny of human natural killer (NK) cells: fetal NK cells mediate cytolytic function and express cytoplasmic CD3 epsilon,delta proteins. J Exp Med. 1992 Apr 1;175(4):1055–1066. doi: 10.1084/jem.175.4.1055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Péault B., Weissman I. L., Baum C., McCune J. M., Tsukamoto A. Lymphoid reconstitution of the human fetal thymus in SCID mice with CD34+ precursor cells. J Exp Med. 1991 Nov 1;174(5):1283–1286. doi: 10.1084/jem.174.5.1283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Schmitt C., Ktorza S., Sarun S., Blanc C., De Jong R., Debre P. CD34-expressing human thymocyte precursors proliferate in response to interleukin-7 but have lost myeloid differentiation potential. Blood. 1993 Dec 15;82(12):3675–3685. [PubMed] [Google Scholar]
  22. Sánchez M. J., Spits H., Lanier L. L., Phillips J. H. Human natural killer cell committed thymocytes and their relation to the T cell lineage. J Exp Med. 1993 Dec 1;178(6):1857–1866. doi: 10.1084/jem.178.6.1857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Terstappen L. W., Huang S., Picker L. J. Flow cytometric assessment of human T-cell differentiation in thymus and bone marrow. Blood. 1992 Feb 1;79(3):666–677. [PubMed] [Google Scholar]
  24. Yssel H., De Vries J. E., Koken M., Van Blitterswijk W., Spits H. Serum-free medium for generation and propagation of functional human cytotoxic and helper T cell clones. J Immunol Methods. 1984 Aug 3;72(1):219–227. doi: 10.1016/0022-1759(84)90450-2. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES