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Functionally mature CD4 and CD8 TCRalphabeta cells are generated in OP9-DL1 cultures from human CD34+ hematopoietic cells.
J Immunol. 2009 Oct 15; 183(8):4859-70.JI

Abstract

Human CD34(+) hematopoietic precursor cells cultured on delta-like ligand 1 expressing OP9 (OP9-DL1) stromal cells differentiate to T lineage cells. The nature of the T cells generated in these cultures has not been studied in detail. Since these cultures do not contain thymic epithelial cells which are the main cell type mediating positive selection in vivo, generation of conventional helper CD4(+) and cytotoxic CD8(+) TCRalphabeta cells is not expected. Phenotypically mature CD27(+)CD1(-) TCRgammadelta as well as TCRalphabeta cells were generated in OP9-DL1 cultures. CD8 and few mature CD4 single-positive TCRalphabeta cells were observed. Mature CD8 single-positive cells consisted of two subpopulations: one expressing mainly CD8alphabeta and one expressing CD8alphaalpha dimers. TCRalphabeta CD8alphaalpha and TCRgammadelta cells both expressed the IL2Rbeta receptor constitutively and proliferated on IL-15, a characteristic of unconventional T cells. CD8alphabeta(+) and CD4(+) TCRalphabeta cells were unresponsive to IL-15, but could be expanded upon TCR stimulation as mature CD8alphabeta(+) and CD4(+) T cells. These T cells had the characteristics of conventional T cells: CD4(+) cells expressed ThPOK, CD40L, and high levels of IL-2 and IL-4; CD8(+) cells expressed Eomes, Runx3, and high levels of granzyme, perforin, and IFN-gamma. Induction of murine or human MHC class I expression on OP9-DL1 cells had no influence on the differentiation of mature CD8(+) cells. Similarly, the presence of dendritic cells was not required for the generation of mature CD4(+) or CD8(+) T cells. These data suggest that positive selection of these cells is induced by interaction between T precursor cells.

Authors+Show Affiliations

Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19801512

Citation

Van Coppernolle, Stefanie, et al. "Functionally Mature CD4 and CD8 TCRalphabeta Cells Are Generated in OP9-DL1 Cultures From Human CD34+ Hematopoietic Cells." Journal of Immunology (Baltimore, Md. : 1950), vol. 183, no. 8, 2009, pp. 4859-70.
Van Coppernolle S, Verstichel G, Timmermans F, et al. Functionally mature CD4 and CD8 TCRalphabeta cells are generated in OP9-DL1 cultures from human CD34+ hematopoietic cells. J Immunol. 2009;183(8):4859-70.
Van Coppernolle, S., Verstichel, G., Timmermans, F., Velghe, I., Vermijlen, D., De Smedt, M., Leclercq, G., Plum, J., Taghon, T., Vandekerckhove, B., & Kerre, T. (2009). Functionally mature CD4 and CD8 TCRalphabeta cells are generated in OP9-DL1 cultures from human CD34+ hematopoietic cells. Journal of Immunology (Baltimore, Md. : 1950), 183(8), 4859-70. https://doi.org/10.4049/jimmunol.0900714
Van Coppernolle S, et al. Functionally Mature CD4 and CD8 TCRalphabeta Cells Are Generated in OP9-DL1 Cultures From Human CD34+ Hematopoietic Cells. J Immunol. 2009 Oct 15;183(8):4859-70. PubMed PMID: 19801512.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functionally mature CD4 and CD8 TCRalphabeta cells are generated in OP9-DL1 cultures from human CD34+ hematopoietic cells. AU - Van Coppernolle,Stefanie, AU - Verstichel,Greet, AU - Timmermans,Frank, AU - Velghe,Imke, AU - Vermijlen,David, AU - De Smedt,Magda, AU - Leclercq,Georges, AU - Plum,Jean, AU - Taghon,Tom, AU - Vandekerckhove,Bart, AU - Kerre,Tessa, PY - 2009/10/6/entrez PY - 2009/10/6/pubmed PY - 2009/11/11/medline SP - 4859 EP - 70 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 183 IS - 8 N2 - Human CD34(+) hematopoietic precursor cells cultured on delta-like ligand 1 expressing OP9 (OP9-DL1) stromal cells differentiate to T lineage cells. The nature of the T cells generated in these cultures has not been studied in detail. Since these cultures do not contain thymic epithelial cells which are the main cell type mediating positive selection in vivo, generation of conventional helper CD4(+) and cytotoxic CD8(+) TCRalphabeta cells is not expected. Phenotypically mature CD27(+)CD1(-) TCRgammadelta as well as TCRalphabeta cells were generated in OP9-DL1 cultures. CD8 and few mature CD4 single-positive TCRalphabeta cells were observed. Mature CD8 single-positive cells consisted of two subpopulations: one expressing mainly CD8alphabeta and one expressing CD8alphaalpha dimers. TCRalphabeta CD8alphaalpha and TCRgammadelta cells both expressed the IL2Rbeta receptor constitutively and proliferated on IL-15, a characteristic of unconventional T cells. CD8alphabeta(+) and CD4(+) TCRalphabeta cells were unresponsive to IL-15, but could be expanded upon TCR stimulation as mature CD8alphabeta(+) and CD4(+) T cells. These T cells had the characteristics of conventional T cells: CD4(+) cells expressed ThPOK, CD40L, and high levels of IL-2 and IL-4; CD8(+) cells expressed Eomes, Runx3, and high levels of granzyme, perforin, and IFN-gamma. Induction of murine or human MHC class I expression on OP9-DL1 cells had no influence on the differentiation of mature CD8(+) cells. Similarly, the presence of dendritic cells was not required for the generation of mature CD4(+) or CD8(+) T cells. These data suggest that positive selection of these cells is induced by interaction between T precursor cells. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/19801512/Functionally_mature_CD4_and_CD8_TCRalphabeta_cells_are_generated_in_OP9_DL1_cultures_from_human_CD34+_hematopoietic_cells_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=19801512 DB - PRIME DP - Unbound Medicine ER -