Hoffmann, Petra and Eder, Ruediger and Boeld, Tina J. and Doser, Kristina and Piseshka, Biserka and Andreesen, Reinhard and Edinger, Matthias (2006) Only the CD45RA(+) subpopulation of CD4(+)CD25(high) T cells gives rise to homogeneous regulatory T-cell lines upon in vitro expansion. BLOOD, 108 (13). pp. 4260-4267. ISSN 0006-4971,
Full text not available from this repository. (Request a copy)Abstract
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(+)CD25(high) T cells maintain phenotypic and functional characteristics of regulatory T cells. Further analysis revealed that these cells originate from D45RA(+) naive cells within the CD4(+)CD25(high) 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(+)CD25(high) 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(+) CD25(high) T cells is the best strategy for adoptive regulatory T (Treg)-cell therapies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; IMMUNOLOGICAL SELF-TOLERANCE; BONE-MARROW-TRANSPLANTATION; SUPPRESSOR FUNCTION; MULTIPLE-SCLEROSIS; ADOPTIVE TRANSFER; IMMUNE-RESPONSE; CUTTING EDGE; LYMPH-NODE; L-SELECTIN; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Jan 2021 12:29 |
| Last Modified: | 15 Jan 2021 13:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33651 |
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