The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation Regimens
Regulatory T cells (Tregs) are essential for the maintenance of tolerance to self and non-self through cell-intrinsic and cell-extrinsic mechanisms. Peripheral Tregs survival and clonal expansion largely depend on IL-2 and access to co-stimulatory signals such as CD28. Engagement of tumor necrosis f...
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MDPI AG
2020-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/9/3347 |
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| author | Jose-Ignacio Rodriguez-Barbosa Pascal Schneider Luis Graca Leo Bühler Jose-Antonio Perez-Simon Maria-Luisa del Rio |
| author_facet | Jose-Ignacio Rodriguez-Barbosa Pascal Schneider Luis Graca Leo Bühler Jose-Antonio Perez-Simon Maria-Luisa del Rio |
| author_sort | Jose-Ignacio Rodriguez-Barbosa |
| collection | DOAJ |
| description | Regulatory T cells (Tregs) are essential for the maintenance of tolerance to self and non-self through cell-intrinsic and cell-extrinsic mechanisms. Peripheral Tregs survival and clonal expansion largely depend on IL-2 and access to co-stimulatory signals such as CD28. Engagement of tumor necrosis factor receptor (TNFR) superfamily members, in particular TNFR2 and DR3, contribute to promote peripheral Tregs expansion and sustain their survival. This property can be leveraged to enhance tolerance to allogeneic transplants by tipping the balance of Tregs over conventional T cells during the course of immune reconstitution. This is of particular interest in peri-transplant tolerance induction protocols in which T cell depletion is applied to reduce the frequency of alloreactive T cells or in conditioning regimens that allow allogeneic bone marrow transplantation. These conditioning regimens are being implemented to limit long-term side effects of continuous immunosuppression and facilitate the establishment of a state of donor-specific tolerance. Lymphopenia-induced homeostatic proliferation in response to cytoreductive conditioning is a window of opportunity to enhance preferential expansion of Tregs during homeostatic proliferation that can be potentiated by agonist stimulation of TNFR. |
| first_indexed | 2024-03-10T19:57:41Z |
| format | Article |
| id | doaj.art-a67bc5f8aea54d9986034ad9a0b78caf |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:57:41Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a67bc5f8aea54d9986034ad9a0b78caf2023-11-19T23:52:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-01219334710.3390/ijms21093347The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation RegimensJose-Ignacio Rodriguez-Barbosa0Pascal Schneider1Luis Graca2Leo Bühler3Jose-Antonio Perez-Simon4Maria-Luisa del Rio5Transplantation Immunobiology, School of Biology and Biotechnology, Institute of Molecular Biology, Genomics and Proteomics, University of Leon, 24071 Leon, SpainDepartment of Biochemistry, University of Lausanne, 1066 Epalinges, SwitzerlandSchool of Medicine, Institute of Molecular Medicine, University of Lisbon, Avenida Professor Egas Moniz, 1649-028 Lisbon, PortugalFaculty of Science and Medicine, Section of Medicine, University of Fribourg, 1700 Fribourg, SwitzerlandDepartment of Hematology, Institute of Biomedicine (IBIS/CSIC), University Hospital Virgen del Rocio, 41013 Sevilla, SpainTransplantation Immunobiology, School of Biology and Biotechnology, Institute of Molecular Biology, Genomics and Proteomics, University of Leon, 24071 Leon, SpainRegulatory T cells (Tregs) are essential for the maintenance of tolerance to self and non-self through cell-intrinsic and cell-extrinsic mechanisms. Peripheral Tregs survival and clonal expansion largely depend on IL-2 and access to co-stimulatory signals such as CD28. Engagement of tumor necrosis factor receptor (TNFR) superfamily members, in particular TNFR2 and DR3, contribute to promote peripheral Tregs expansion and sustain their survival. This property can be leveraged to enhance tolerance to allogeneic transplants by tipping the balance of Tregs over conventional T cells during the course of immune reconstitution. This is of particular interest in peri-transplant tolerance induction protocols in which T cell depletion is applied to reduce the frequency of alloreactive T cells or in conditioning regimens that allow allogeneic bone marrow transplantation. These conditioning regimens are being implemented to limit long-term side effects of continuous immunosuppression and facilitate the establishment of a state of donor-specific tolerance. Lymphopenia-induced homeostatic proliferation in response to cytoreductive conditioning is a window of opportunity to enhance preferential expansion of Tregs during homeostatic proliferation that can be potentiated by agonist stimulation of TNFR.https://www.mdpi.com/1422-0067/21/9/3347regulatory T cellslymphopeniahomeostatic proliferationtransplantationTNF/TNF receptorsgraft-versus-host disease |
| spellingShingle | Jose-Ignacio Rodriguez-Barbosa Pascal Schneider Luis Graca Leo Bühler Jose-Antonio Perez-Simon Maria-Luisa del Rio The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation Regimens International Journal of Molecular Sciences regulatory T cells lymphopenia homeostatic proliferation transplantation TNF/TNF receptors graft-versus-host disease |
| title | The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation Regimens |
| title_full | The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation Regimens |
| title_fullStr | The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation Regimens |
| title_full_unstemmed | The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation Regimens |
| title_short | The Role of TNFR2 and DR3 in the In Vivo Expansion of Tregs in T Cell Depleting Transplantation Regimens |
| title_sort | role of tnfr2 and dr3 in the in vivo expansion of tregs in t cell depleting transplantation regimens |
| topic | regulatory T cells lymphopenia homeostatic proliferation transplantation TNF/TNF receptors graft-versus-host disease |
| url | https://www.mdpi.com/1422-0067/21/9/3347 |
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