Polyclonal Recipient nTregs Are Superior to Donor or Third-Party Tregs in the Induction of Transplantation Tolerance
Induction of donor-specific tolerance is still considered as the “Holy Grail” in transplantation medicine. The mixed chimerism approach is virtually the only tolerance approach that was successfully translated into the clinical setting. We have previously reported successful induction of chimerism a...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2015-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2015/562935 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832549280786677760 |
|---|---|
| author | Nina Pilat Christoph Klaus Karin Hock Ulrike Baranyi Lukas Unger Benedikt Mahr Andreas M. Farkas Fritz Wrba Thomas Wekerle |
| author_facet | Nina Pilat Christoph Klaus Karin Hock Ulrike Baranyi Lukas Unger Benedikt Mahr Andreas M. Farkas Fritz Wrba Thomas Wekerle |
| author_sort | Nina Pilat |
| collection | DOAJ |
| description | Induction of donor-specific tolerance is still considered as the “Holy Grail” in transplantation medicine. The mixed chimerism approach is virtually the only tolerance approach that was successfully translated into the clinical setting. We have previously reported successful induction of chimerism and tolerance using cell therapy with recipient T regulatory cells (Tregs) to avoid cytotoxic recipient treatment. Treg therapy is limited by the availability of cells as large-scale expansion is time-consuming and associated with the risk of contamination with effector cells. Using a costimulation-blockade based bone marrow (BM) transplantation (BMT) model with Treg therapy instead of cytoreductive recipient treatment we aimed to determine the most potent Treg population for clinical translation. Here we show that CD4+CD25+ in vitro activated nTregs are superior to TGFβ induced iTregs in promoting the induction of chimerism and tolerance. Therapy with nTregs (but not iTregs) led to multilineage chimerism and donor-specific tolerance in mice receiving as few as 0.5 × 106 cells. Moreover, we show that only recipient Tregs, but not donor or third-party Tregs, had a beneficial effect on BM engraftment at the tested doses. Thus, recipient-type nTregs significantly improve chimerism and tolerance and might be the most potent Treg population for translation into the clinical setting. |
| format | Article |
| id | doaj-art-03978fb2ddc248a5a3005addf9ccdc56 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-03978fb2ddc248a5a3005addf9ccdc562025-02-03T06:11:40ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/562935562935Polyclonal Recipient nTregs Are Superior to Donor or Third-Party Tregs in the Induction of Transplantation ToleranceNina Pilat0Christoph Klaus1Karin Hock2Ulrike Baranyi3Lukas Unger4Benedikt Mahr5Andreas M. Farkas6Fritz Wrba7Thomas Wekerle8Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, 1090 Vienna, AustriaSection of Transplantation Immunology, Department of Surgery, Medical University of Vienna, 1090 Vienna, AustriaSection of Transplantation Immunology, Department of Surgery, Medical University of Vienna, 1090 Vienna, AustriaSection of Transplantation Immunology, Department of Surgery, Medical University of Vienna, 1090 Vienna, AustriaSection of Transplantation Immunology, Department of Surgery, Medical University of Vienna, 1090 Vienna, AustriaSection of Transplantation Immunology, Department of Surgery, Medical University of Vienna, 1090 Vienna, AustriaSection of Transplantation Immunology, Department of Surgery, Medical University of Vienna, 1090 Vienna, AustriaInstitute of Clinical Pathology, Medical University of Vienna, 1090 Vienna, AustriaSection of Transplantation Immunology, Department of Surgery, Medical University of Vienna, 1090 Vienna, AustriaInduction of donor-specific tolerance is still considered as the “Holy Grail” in transplantation medicine. The mixed chimerism approach is virtually the only tolerance approach that was successfully translated into the clinical setting. We have previously reported successful induction of chimerism and tolerance using cell therapy with recipient T regulatory cells (Tregs) to avoid cytotoxic recipient treatment. Treg therapy is limited by the availability of cells as large-scale expansion is time-consuming and associated with the risk of contamination with effector cells. Using a costimulation-blockade based bone marrow (BM) transplantation (BMT) model with Treg therapy instead of cytoreductive recipient treatment we aimed to determine the most potent Treg population for clinical translation. Here we show that CD4+CD25+ in vitro activated nTregs are superior to TGFβ induced iTregs in promoting the induction of chimerism and tolerance. Therapy with nTregs (but not iTregs) led to multilineage chimerism and donor-specific tolerance in mice receiving as few as 0.5 × 106 cells. Moreover, we show that only recipient Tregs, but not donor or third-party Tregs, had a beneficial effect on BM engraftment at the tested doses. Thus, recipient-type nTregs significantly improve chimerism and tolerance and might be the most potent Treg population for translation into the clinical setting.http://dx.doi.org/10.1155/2015/562935 |
| spellingShingle | Nina Pilat Christoph Klaus Karin Hock Ulrike Baranyi Lukas Unger Benedikt Mahr Andreas M. Farkas Fritz Wrba Thomas Wekerle Polyclonal Recipient nTregs Are Superior to Donor or Third-Party Tregs in the Induction of Transplantation Tolerance Journal of Immunology Research |
| title | Polyclonal Recipient nTregs Are Superior to Donor or Third-Party Tregs in the Induction of Transplantation Tolerance |
| title_full | Polyclonal Recipient nTregs Are Superior to Donor or Third-Party Tregs in the Induction of Transplantation Tolerance |
| title_fullStr | Polyclonal Recipient nTregs Are Superior to Donor or Third-Party Tregs in the Induction of Transplantation Tolerance |
| title_full_unstemmed | Polyclonal Recipient nTregs Are Superior to Donor or Third-Party Tregs in the Induction of Transplantation Tolerance |
| title_short | Polyclonal Recipient nTregs Are Superior to Donor or Third-Party Tregs in the Induction of Transplantation Tolerance |
| title_sort | polyclonal recipient ntregs are superior to donor or third party tregs in the induction of transplantation tolerance |
| url | http://dx.doi.org/10.1155/2015/562935 |
| work_keys_str_mv | AT ninapilat polyclonalrecipientntregsaresuperiortodonororthirdpartytregsintheinductionoftransplantationtolerance AT christophklaus polyclonalrecipientntregsaresuperiortodonororthirdpartytregsintheinductionoftransplantationtolerance AT karinhock polyclonalrecipientntregsaresuperiortodonororthirdpartytregsintheinductionoftransplantationtolerance AT ulrikebaranyi polyclonalrecipientntregsaresuperiortodonororthirdpartytregsintheinductionoftransplantationtolerance AT lukasunger polyclonalrecipientntregsaresuperiortodonororthirdpartytregsintheinductionoftransplantationtolerance AT benediktmahr polyclonalrecipientntregsaresuperiortodonororthirdpartytregsintheinductionoftransplantationtolerance AT andreasmfarkas polyclonalrecipientntregsaresuperiortodonororthirdpartytregsintheinductionoftransplantationtolerance AT fritzwrba polyclonalrecipientntregsaresuperiortodonororthirdpartytregsintheinductionoftransplantationtolerance AT thomaswekerle polyclonalrecipientntregsaresuperiortodonororthirdpartytregsintheinductionoftransplantationtolerance |