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Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells
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| Zeitschriftentitel: | Blood |
|---|---|
| Personen und Körperschaften: | , , , , |
| In: | Blood, 104, 2004, 3, S. 895-903 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Hematology
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| Schlagwörter: |
| author_facet |
Hoffmann, Petra Eder, Ruediger Kunz-Schughart, Leoni A. Andreesen, Reinhard Edinger, Matthias Hoffmann, Petra Eder, Ruediger Kunz-Schughart, Leoni A. Andreesen, Reinhard Edinger, Matthias |
|---|---|
| author |
Hoffmann, Petra Eder, Ruediger Kunz-Schughart, Leoni A. Andreesen, Reinhard Edinger, Matthias |
| spellingShingle |
Hoffmann, Petra Eder, Ruediger Kunz-Schughart, Leoni A. Andreesen, Reinhard Edinger, Matthias Blood Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells Cell Biology Hematology Immunology Biochemistry |
| author_sort |
hoffmann, petra |
| spelling |
Hoffmann, Petra Eder, Ruediger Kunz-Schughart, Leoni A. Andreesen, Reinhard Edinger, Matthias 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood-2004-01-0086 <jats:title>Abstract</jats:title><jats:p>CD4+CD25+ regulatory T (Treg) cells are pivotal for the maintenance of self-tolerance, and their adoptive transfer gives protection from autoimmune diseases and pathogenic alloresponses after solid organ or bone marrow transplantation in murine model systems. In vitro, human CD4+CD25+ Treg cells display phenotypic and functional characteristics similar to those of murine CD4+CD25+ Treg cells: namely, hyporesponsiveness to T-cell receptor (TCR) stimulation and suppression of CD25- T cells. Thus far, the detailed characterization and potential clinical application of human CD4+CD25+ Treg cells have been hampered by their paucity in peripheral blood and the lack of appropriate expansion protocols. Here we describe the up to 40 000-fold expansion of highly purified human CD4+CD25high T cells in vitro through the use of artificial antigen-presenting cells for repeated stimulation via CD3 and CD28 in the presence of high-dose interleukin 2 (IL-2). Expanded CD4+CD25high T cells were polyclonal, maintained their phenotype, exceeded the suppressive activity of freshly isolated CD4+CD25high T cells, and maintained expression of the lymph node homing receptors L-selectin (CD62L) and CCR7. The ability to rapidly expand human CD4+CD25high Treg cells on a large scale will not only facilitate their further exploration but also accelerate their potential clinical application in T cell–mediated diseases and transplantation medicine.</jats:p> Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells Blood |
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10.1182/blood-2004-01-0086 |
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American Society of Hematology, 2004 |
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American Society of Hematology, 2004 |
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0006-4971 1528-0020 |
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0006-4971 1528-0020 |
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| title |
Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells |
| title_unstemmed |
Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells |
| title_full |
Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells |
| title_fullStr |
Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells |
| title_full_unstemmed |
Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells |
| title_short |
Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells |
| title_sort |
large-scale in vitro expansion of polyclonal human cd4+cd25high regulatory t cells |
| topic |
Cell Biology Hematology Immunology Biochemistry |
| url |
http://dx.doi.org/10.1182/blood-2004-01-0086 |
| publishDate |
2004 |
| physical |
895-903 |
| description |
<jats:title>Abstract</jats:title><jats:p>CD4+CD25+ regulatory T (Treg) cells are pivotal for the maintenance of self-tolerance, and their adoptive transfer gives protection from autoimmune diseases and pathogenic alloresponses after solid organ or bone marrow transplantation in murine model systems. In vitro, human CD4+CD25+ Treg cells display phenotypic and functional characteristics similar to those of murine CD4+CD25+ Treg cells: namely, hyporesponsiveness to T-cell receptor (TCR) stimulation and suppression of CD25- T cells. Thus far, the detailed characterization and potential clinical application of human CD4+CD25+ Treg cells have been hampered by their paucity in peripheral blood and the lack of appropriate expansion protocols. Here we describe the up to 40 000-fold expansion of highly purified human CD4+CD25high T cells in vitro through the use of artificial antigen-presenting cells for repeated stimulation via CD3 and CD28 in the presence of high-dose interleukin 2 (IL-2). Expanded CD4+CD25high T cells were polyclonal, maintained their phenotype, exceeded the suppressive activity of freshly isolated CD4+CD25high T cells, and maintained expression of the lymph node homing receptors L-selectin (CD62L) and CCR7. The ability to rapidly expand human CD4+CD25high Treg cells on a large scale will not only facilitate their further exploration but also accelerate their potential clinical application in T cell–mediated diseases and transplantation medicine.</jats:p> |
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| author | Hoffmann, Petra, Eder, Ruediger, Kunz-Schughart, Leoni A., Andreesen, Reinhard, Edinger, Matthias |
| author_facet | Hoffmann, Petra, Eder, Ruediger, Kunz-Schughart, Leoni A., Andreesen, Reinhard, Edinger, Matthias, Hoffmann, Petra, Eder, Ruediger, Kunz-Schughart, Leoni A., Andreesen, Reinhard, Edinger, Matthias |
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| description | <jats:title>Abstract</jats:title><jats:p>CD4+CD25+ regulatory T (Treg) cells are pivotal for the maintenance of self-tolerance, and their adoptive transfer gives protection from autoimmune diseases and pathogenic alloresponses after solid organ or bone marrow transplantation in murine model systems. In vitro, human CD4+CD25+ Treg cells display phenotypic and functional characteristics similar to those of murine CD4+CD25+ Treg cells: namely, hyporesponsiveness to T-cell receptor (TCR) stimulation and suppression of CD25- T cells. Thus far, the detailed characterization and potential clinical application of human CD4+CD25+ Treg cells have been hampered by their paucity in peripheral blood and the lack of appropriate expansion protocols. Here we describe the up to 40 000-fold expansion of highly purified human CD4+CD25high T cells in vitro through the use of artificial antigen-presenting cells for repeated stimulation via CD3 and CD28 in the presence of high-dose interleukin 2 (IL-2). Expanded CD4+CD25high T cells were polyclonal, maintained their phenotype, exceeded the suppressive activity of freshly isolated CD4+CD25high T cells, and maintained expression of the lymph node homing receptors L-selectin (CD62L) and CCR7. The ability to rapidly expand human CD4+CD25high Treg cells on a large scale will not only facilitate their further exploration but also accelerate their potential clinical application in T cell–mediated diseases and transplantation medicine.</jats:p> |
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| imprint | American Society of Hematology, 2004 |
| imprint_str_mv | American Society of Hematology, 2004 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Rs1, DE-Pl11, DE-105, DE-14, DE-Ch1, DE-L229 |
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| spelling | Hoffmann, Petra Eder, Ruediger Kunz-Schughart, Leoni A. Andreesen, Reinhard Edinger, Matthias 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood-2004-01-0086 <jats:title>Abstract</jats:title><jats:p>CD4+CD25+ regulatory T (Treg) cells are pivotal for the maintenance of self-tolerance, and their adoptive transfer gives protection from autoimmune diseases and pathogenic alloresponses after solid organ or bone marrow transplantation in murine model systems. In vitro, human CD4+CD25+ Treg cells display phenotypic and functional characteristics similar to those of murine CD4+CD25+ Treg cells: namely, hyporesponsiveness to T-cell receptor (TCR) stimulation and suppression of CD25- T cells. Thus far, the detailed characterization and potential clinical application of human CD4+CD25+ Treg cells have been hampered by their paucity in peripheral blood and the lack of appropriate expansion protocols. Here we describe the up to 40 000-fold expansion of highly purified human CD4+CD25high T cells in vitro through the use of artificial antigen-presenting cells for repeated stimulation via CD3 and CD28 in the presence of high-dose interleukin 2 (IL-2). Expanded CD4+CD25high T cells were polyclonal, maintained their phenotype, exceeded the suppressive activity of freshly isolated CD4+CD25high T cells, and maintained expression of the lymph node homing receptors L-selectin (CD62L) and CCR7. The ability to rapidly expand human CD4+CD25high Treg cells on a large scale will not only facilitate their further exploration but also accelerate their potential clinical application in T cell–mediated diseases and transplantation medicine.</jats:p> Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells Blood |
| spellingShingle | Hoffmann, Petra, Eder, Ruediger, Kunz-Schughart, Leoni A., Andreesen, Reinhard, Edinger, Matthias, Blood, Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells, Cell Biology, Hematology, Immunology, Biochemistry |
| title | Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells |
| title_full | Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells |
| title_fullStr | Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells |
| title_full_unstemmed | Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells |
| title_short | Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells |
| title_sort | large-scale in vitro expansion of polyclonal human cd4+cd25high regulatory t cells |
| title_unstemmed | Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells |
| topic | Cell Biology, Hematology, Immunology, Biochemistry |
| url | http://dx.doi.org/10.1182/blood-2004-01-0086 |