Adoptive transfer of antigen specific regulatory T (Treg) cells was shown to be beneficial for the suppression of autoimmunity. In this study, we engineered antigen-specific Treg-like cells that recognise mouse MHC-class II molecules. The restricted expression of MHCII to professional antigen presenting cells and to inflammatory sites, allow the employment of MHCII specific Treg for suppression of unwanted immune inflammation. A mouse MHCII-specific Chimeric Antigen Receptor (CAR) was used to redirect the specificity of T cells via retroviral transduction, while Foxp3 gene transfer into purified CD4+ cells leads to the acquisition of a Treg-like phenotype. Incorporation of a suicide mechanism within the engineered Treg-like cells for their in vivo selective deletion will prevent long-term immune suppression. The functionality of the generated CAR and the specificity of responses elicited by CAR bearing T cells were validated in vitro. In preliminary in vivo experiments, intravenous injection of C57BL/6 mice with syngeneic mouse MHCII-specific CD4+ T cells, led to GVHD-like toxicity, while no signs of toxicity were observed when Treg-like cells of the same specificity were transferred alone or in a 1:1 mix with mouse MHCII specific CD4+ T cells. These data suggest the suppressive potential of the engineered Treg-like cells.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:746216 |
| Date | January 2016 |
| Creators | Stavrou, M. |
| Contributors | Stauss, H. ; Pule, M. ; Shlomchik, W. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1503502/ |
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