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Obtaining regulatory T cells from uraemic patients awaiting kidney transplantation for use in clinical trials

Berglund, D ; Karlsson, M ; Biglarnia, A-R LU orcid ; Lorant, T ; Tufveson, G ; Korsgren, O and Carlsson, B (2013) In Clinical and Experimental Immunology 173(2). p.22-310
Abstract

Adoptive transfer of regulatory T cells (T(regs)) has been proposed for use as a cellular therapy to induce transplantation tolerance. Preclinical data are encouraging, and clinical trials with T(reg) therapy are anticipated. In this study, we investigate different strategies for the isolation and expansion of CD4(+) CD25(high) CD127(low) T(regs) from uraemic patients. We use allogeneic dendritic cells (DCs) as feeder cells for the expansion and compare T(reg) preparations isolated by either fluorescence activated cell sorting (FACS) or magnetic activated cell sorting (MACS) that have been expanded subsequently with either mature or tolerogenic DCs. Expanded T(reg) preparations have been characterized by their purity, cytokine... (More)

Adoptive transfer of regulatory T cells (T(regs)) has been proposed for use as a cellular therapy to induce transplantation tolerance. Preclinical data are encouraging, and clinical trials with T(reg) therapy are anticipated. In this study, we investigate different strategies for the isolation and expansion of CD4(+) CD25(high) CD127(low) T(regs) from uraemic patients. We use allogeneic dendritic cells (DCs) as feeder cells for the expansion and compare T(reg) preparations isolated by either fluorescence activated cell sorting (FACS) or magnetic activated cell sorting (MACS) that have been expanded subsequently with either mature or tolerogenic DCs. Expanded T(reg) preparations have been characterized by their purity, cytokine production and in-vitro suppressive ability. The results show that T(reg) preparations can be isolated from uraemic patients by both FACS and MACS. Also, the type of feeder cells used in the expansion affects both the purity and the functional properties of the T(reg) preparations. In particular, FACS-sorted T(reg) preparations expanded with mature DCs secrete more interleukin (IL)-10 and granzyme B than FACS-sorted T(reg) preparations expanded with tolerogenic DCs. This is a direct comparison between different isolation techniques and expansion protocols with T(regs) from uraemic patients that may guide future efforts to produce clinical-grade T(regs) for use in kidney transplantation.

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author
; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
CD4 Antigens/metabolism, Cell Culture Techniques/methods, Cell Growth Processes, Cell Separation, Cells, Cultured, Cytokines/metabolism, Dendritic Cells/immunology, Flow Cytometry, HLA Antigens/immunology, Humans, Immunosuppression Therapy, Immunotherapy, Adoptive/methods, Interleukin-2 Receptor alpha Subunit/metabolism, Interleukin-7 Receptor alpha Subunit/metabolism, Kidney Diseases/immunology, Kidney Transplantation, Practice Guidelines as Topic, T-Lymphocytes, Regulatory/immunology, Transplantation Tolerance, Waiting Lists
in
Clinical and Experimental Immunology
volume
173
issue
2
pages
22 - 310
publisher
Oxford University Press
external identifiers
  • scopus:84880021002
  • pmid:23607776
ISSN
0009-9104
DOI
10.1111/cei.12112
language
English
LU publication?
no
additional info
© 2013 British Society for Immunology.
id
088a54b0-ee3e-4b05-8062-44cc3de317b0
date added to LUP
2025-12-17 14:16:54
date last changed
2025-12-19 02:25:41
@article{088a54b0-ee3e-4b05-8062-44cc3de317b0,
  abstract     = {{<p>Adoptive transfer of regulatory T cells (T(regs)) has been proposed for use as a cellular therapy to induce transplantation tolerance. Preclinical data are encouraging, and clinical trials with T(reg) therapy are anticipated. In this study, we investigate different strategies for the isolation and expansion of CD4(+) CD25(high) CD127(low) T(regs) from uraemic patients. We use allogeneic dendritic cells (DCs) as feeder cells for the expansion and compare T(reg) preparations isolated by either fluorescence activated cell sorting (FACS) or magnetic activated cell sorting (MACS) that have been expanded subsequently with either mature or tolerogenic DCs. Expanded T(reg) preparations have been characterized by their purity, cytokine production and in-vitro suppressive ability. The results show that T(reg) preparations can be isolated from uraemic patients by both FACS and MACS. Also, the type of feeder cells used in the expansion affects both the purity and the functional properties of the T(reg) preparations. In particular, FACS-sorted T(reg) preparations expanded with mature DCs secrete more interleukin (IL)-10 and granzyme B than FACS-sorted T(reg) preparations expanded with tolerogenic DCs. This is a direct comparison between different isolation techniques and expansion protocols with T(regs) from uraemic patients that may guide future efforts to produce clinical-grade T(regs) for use in kidney transplantation.</p>}},
  author       = {{Berglund, D and Karlsson, M and Biglarnia, A-R and Lorant, T and Tufveson, G and Korsgren, O and Carlsson, B}},
  issn         = {{0009-9104}},
  keywords     = {{CD4 Antigens/metabolism; Cell Culture Techniques/methods; Cell Growth Processes; Cell Separation; Cells, Cultured; Cytokines/metabolism; Dendritic Cells/immunology; Flow Cytometry; HLA Antigens/immunology; Humans; Immunosuppression Therapy; Immunotherapy, Adoptive/methods; Interleukin-2 Receptor alpha Subunit/metabolism; Interleukin-7 Receptor alpha Subunit/metabolism; Kidney Diseases/immunology; Kidney Transplantation; Practice Guidelines as Topic; T-Lymphocytes, Regulatory/immunology; Transplantation Tolerance; Waiting Lists}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{22--310}},
  publisher    = {{Oxford University Press}},
  series       = {{Clinical and Experimental Immunology}},
  title        = {{Obtaining regulatory T cells from uraemic patients awaiting kidney transplantation for use in clinical trials}},
  url          = {{http://dx.doi.org/10.1111/cei.12112}},
  doi          = {{10.1111/cei.12112}},
  volume       = {{173}},
  year         = {{2013}},
}