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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 04312nam a2200409 4500 | |
| 001 | oai:DiVA.org:uu-220873 | |
| 003 | SwePub | |
| 008 | 140321s2014 | |||||||||||000 ||eng| | |
| 020 | a 9789155489076q print | |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2208732 URI |
| 040 | a (SwePub)uu | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a vet2 swepub-contenttype |
| 072 | 7 | a dok2 swepub-publicationtype |
| 100 | 1 | a Berglund, David,d 1984-u Uppsala universitet,Klinisk immunologi,Transplantationskirurgi4 aut0 (Swepub:uu)davbe892 |
| 245 | 1 0 | a Preparatory Studies to Introduce Regulatory T Cells in Clinical Transplantation |
| 264 | 1 | a Uppsala :b Acta Universitatis Upsaliensis,c 2014 |
| 300 | a 80 s. | |
| 338 | a electronic2 rdacarrier | |
| 490 | 0 | a Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine,x 1651-6206 ;v 983 |
| 520 | a Solid organ transplantation has evolved from being an experimental procedure to a life-saving treatment for patients with end-stage organ failure. The risk of losing a transplant due to acute rejection is very low with the use of modern immunosuppressive protocols and the short-term results are impressive. However, long-term outcomes are suboptimal and transplant recipients are at increased risks for severe complications such as cancers, opportunistic infections and cardiovascular events. The previous struggle to achieve short-term survival has turned into a search for new strategies to improve patient and transplant longevity.Regulatory T cells (TRegs), a subset of T cells, occur naturally in the immune system and have the capacity to down regulate immune responses. Under normal conditions they maintain self-tolerance and prevent excessive immune activation. Functional TReg defects lead to a massive autoimmune response and are not compatible with life. Preclinical data support that TRegs can be used as a cell therapy to prevent transplant rejection, with the potential to minimize the need for traditional immunosuppression and improve the long-term outcome.This thesis aims to enhance the translation of TReg cell therapy to clinical organ transplantation. In particular, strategies for isolation and expansion of TRegs from uremic patients awaiting kidney transplantation have been assessed. A non-invasive imaging technique to study T cell products after intravenous administration was developed, for use in future clinical trials. The performance of a novel cell purification technique was investigated to potentially improve the clinical production of TRegs.The thesis demonstrates that TRegs can be isolated and expanded from uremic patients to display potent suppressive properties in vitro. The mode of isolation and expansion affect the functional characteristics, where cells purified with cytometry based techniques and expanded with mature dendritic cells were the most advantageous. T cells can be labeled using the radioactive tracer [111In]oxine with preserved viability and subsequently followed in vivo with SPECT/CT for more than 1 week after intravenous administration. The use of microfluidic switch technology offers a novel way of purifying TRegs at high speed, purity and viability, under conditions compatible with clinical use. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Immunologi inom det medicinska området0 (SwePub)301102 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Immunology in the medical area0 (SwePub)301102 hsv//eng |
| 653 | a Transplantation | |
| 653 | a Tolerance | |
| 653 | a Cell therapy | |
| 653 | a Regulatory T cell | |
| 653 | a In vivo imaging | |
| 653 | a Cell purification | |
| 700 | 1 | a Tufveson, Gunnar,c Professoru Uppsala universitet,Transplantationskirurgi4 ths |
| 700 | 1 | a Korsgren, Olleu Uppsala universitet,Klinisk immunologi4 ths |
| 700 | 1 | a Sachs, David,c Professoru Harvard University4 opn |
| 710 | 2 | a Uppsala universitetb Klinisk immunologi4 org |
| 856 | 4 | u https://uu.diva-portal.org/smash/get/diva2:706830/FULLTEXT01.pdfx primaryx Raw objecty fulltext |
| 856 | 4 | u https://uu.diva-portal.org/smash/get/diva2:706830/PREVIEW01.jpgx Previewy preview image |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-220873 |
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