Abstract
We report that the mononuclear cells of human cord blood contain a cell population that support the differentiation of CD34+ cells into CD4+ or CD8+ naive T-cells in serum-deprived cultures stimulated with stem cell factor and interleukin 7. CD4+ or CD8+ CD45RA+ TCRαβ+ T-cells are continuously produced in vitro over a period of 20 days under these conditions. The generation of T cells in these cultures is a dynamic process and clones of T cells expressing new T-cell receptor β-chain rearrangments are generated over time. These results pave the way to the development of very simple culture conditions for ex-vivo production of naive helper or cytotoxic T-cells which could be very useful for gene and immune therapy of human diseases.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Lieberman J, Skolnik PR, Parkerson GR, Fabry JA, Landry B, Bethel J, Kagan J: Safety of autologous, ex vivo-expanded human immunodeficiency virus (HlV)-specific cytotoxic T-lymphocyte infusion in HIV-infected patients. Blood 90: 2196, 1997.
Chang AE, Shu S: Current status of adoptive immunotherapy of cancer. Crit.Rev.Oncol.Hematol. 22: 213, 1996.
Rosenzweig M, Marks DF, Hempel D, Johnson RP: In vitro T lymphopoiesis: a model system for stem cell gene therapy for AIDS. J.Med.Primatol. 25: 192, 1996.
An DS, Koyanagi Y, Zhao JQ, Akkina R, Bristol G, Yamamoto N, Zack JA, Chen IS: High-efficiency transduction of human lymphoid progenitor cells and expression in differentiated T cells. J.Virol. 71: 1397, 1997.
Freedman AR, Zhu H, Levine JD, Kalams S, Scadden DT: Generation of human T lymphocytes from bone marrow CD34+ cells in vitro. Nat.Med. 2: 46, 1996.
Krowka JF, Sarin S, Namikawa R, McCune JM, Kaneshima H: Human T cells in the SCID-hu mouse are phenotypically normal and functionally competent. J.Immunol. 146: 3751, 1991.
Plum J, De Smedt M, Defresne M-P, Leclercq G, Vandekerckhove BA: Human CD34+ fetal liver stem cells differentiate to T cells in a mouse thymic microenvironment. Blood 84: 1587, 1994.
Yeoman H, Clark DR, Deluca D: Development of CD4 and CD8 single positive T cells in human thymus organ culture: IL-7 promotes human T cell production by supporting immature T cells. Dev.Comp.Immunol 20: 241, 1996.
Tagoh H, Kishi H, Okumura A, Kitagawa T, Nagata T, Mori K, Muraguchi A: Induction of recombination activating gene expression in a human lymphoid progenitor cell line: requirement of two separate signals from stromal cells and cytokines. Blood 88: 4463, 1996.
Broxmeyer HE, Hangoc G, Cooper S, Ribeiro RC, Graves V, Yoder M, Wagner JE. Vadhan-Raj S, Benninger L, Rubinstein P, Broun ER: Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults. Proc.Natl.Acad.Sci.U.S.A. 89: 4109, 1992.
Blom B, Res P, Noteboom E, Weijer K, Spits H: Prethymic CD34+ progenitors capable of developing into T cells are not committed to the T cell lineage. J.Immunol. 158: 3571, 1997.
Migliaccio G, Migliaccio AR, Druzin ML, Giardina PJ, Zsebo KM, Adamson JW: Long-term generation of colony-forming cells in liquid culture of CD34+ cord blood cells in the presence of recombinant human stem cell factor. Blood 79: 2620, 1992.
Choi Y, Kotzin B, Herron L, Callahan J, Marrack P, Kappler J: Interaction of Staphylococcus aureus toxin “superantigens” with human T-cells. Proc.Natl.Acad.Sci.U.S.A. 86: 8941, 1989.
Peault B: In-vitro models of stroma-dependent lymphopoiesis. Semin.Immunol. 7: 169, 1995.
Anderson G, Moore NC, Owen JJT, Jenkinson EJ: Cellular interactions in thymocyte development. Annu.Rev.Immunol. 14: 73, 1996.
Yurasov S, Kollmann TR, Kim A, Raker CA, Hachamovitch M, Wong Staal F. Goldstein H: Severe combined immunodeficiency mice engrafted with human T cells, B Cells, and myeloid cells after transplantation with human fetal bone marrow or liver cells and implanted with human fetal thymus: a model for studying human gene therapy. Blood 89: 1800, 1997.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer Science+Business Media New York
About this chapter
Cite this chapter
Sanchez, M., Alfani, E., Visconti, G., Passarelli, A.M., Migliaccio, A.R., Migliaccio, G. (1999). Thymus-Independent T Cell Differentiation in Vitro . In: Abraham, N.G., Tabilio, A., Martelli, M., Asano, S., Donfrancesco, A. (eds) Molecular Biology of Hematopoiesis 6. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4797-6_6
Download citation
DOI: https://doi.org/10.1007/978-1-4615-4797-6_6
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7173-1
Online ISBN: 978-1-4615-4797-6
eBook Packages: Springer Book Archive