Hoffmann, Petra, Eder, Ruediger, Boeld, Tina J, Doser, Kristina, Piseshka, Biserka, Andreesen, Reinhard und Edinger, Matthias
(2006)
Only the CD45RA+ subpopulation of CD4+CD25high T cells gives rise to homogeneous regulatory T-cell lines upon in vitro expansion.
Blood 108 (13), S. 4260-7.
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Zusammenfassung
Thymus-derived CD4+ CD25+ regulatory T cells suppress autoreactive CD4+ and CD8+ T cells and thereby protect from autoimmunity. In animal models, adoptive transfer of CD4+ CD25+ regulatory T cells has been shown to prevent and even cure autoimmune diseases as well as pathogenic alloresponses after solid organ and stem-cell transplantations. We recently described methods for the efficient in vitro ...
Zusammenfassung
Thymus-derived CD4+ CD25+ regulatory T cells suppress autoreactive CD4+ and CD8+ T cells and thereby protect from autoimmunity. In animal models, adoptive transfer of CD4+ CD25+ regulatory T cells has been shown to prevent and even cure autoimmune diseases as well as pathogenic alloresponses after solid organ and stem-cell transplantations. We recently described methods for the efficient in vitro expansion of human regulatory T cells for clinical applications. We now demonstrate that only CCR7- and L-selectin (CD62L)-coexpressing cells within expanded CD4+ CD25high T cells maintain phenotypic and functional characteristics of regulatory T cells. Further analysis revealed that these cells originate from CD45RA+ naive cells within the CD4+ CD25high T-cell compartment, as only this subpopulation homogeneously expressed CD62L, CCR7, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), and forkhead box P3 (FOXP3), produced no inflammatory cytokines and maintained robust suppressive activity after expansion. In contrast, cell lines derived from CD45RA- memory-type CD4+ CD25high T cells lost expression of lymph node homing receptors CCR7 and CD62L, contained interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) as well as IL-10-secreting cells, showed only moderate suppression and, most importantly, did not maintain FOXP3 expression. Based on these unexpected findings, we suggest that isolation and expansion of CD45RA+ naive CD4+ CD25high T cells is the best strategy for adoptive regulatory T (Treg)-cell therapies.
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| Dokumentenart: | Artikel |
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| Datum: | 2006 |
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| Institutionen: | Medizin > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
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| Identifikationsnummer: | | Wert | Typ |
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| 16917003 | PubMed-ID | | 10.1182/blood-2006-06-027409 | DOI |
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| Klassifikation: | | Notation | Art |
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| Antigens, CD/immunology | MESH | | Antigens, CD45/immunology | MESH | | Antigens, Differentiation/immunology | MESH | | Cell Differentiation/immunology | MESH | | Cell Proliferation | MESH | | Cells, Cultured | MESH | | Cytokines/immunology | MESH | | Female | MESH | | Forkhead Transcription Factors/immunology | MESH | | Gene Expression Regulation/immunology | MESH | | Humans | MESH | | Immunotherapy, Adoptive | MESH | | L-Selectin/immunology | MESH | | Male | MESH | | Receptors, CCR7 | MESH | | Receptors, Chemokine/immunology | MESH | | T-Lymphocytes, Regulatory/metabolism | MESH | | Thymus Gland/metabolism | MESH |
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| Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin |
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| Status: | Veröffentlicht |
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| Begutachtet: | Ja, diese Version wurde begutachtet |
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| An der Universität Regensburg entstanden: | Ja |
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| Eingebracht am: | 20 Apr 2010 09:37 |
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| Zuletzt geändert: | 24 Mai 2018 12:01 |
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| Dokumenten-ID: | 14488 |
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