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Effect Of Donor-recipient Chimeric Cells Therapy On T Regulatory Cells Population, Chimerism Level And Tolerogenic Factors Gene Expression In Face Allograft Model
Joanna Cwykiel, Fatih Zor, Aleksandra Klimczak, Maria Siemionow
Cleveland Clinic
2010-04-01
Presenter: Joanna Cwykiel
Affidavit:
Director Name:
Author Category: Resident/Fellow
Presentation Category: Basic Science Research
Abstract Category: Craniomaxillofacial
Introduction
Using face allo-transplantation model under donor-recipient chimeric cell therapy we determined gene expression of factors (Il-10, Tgfâ, FoxP3) which play a role in allograft survival and their correlation with changes in Treg cell population and chimerism level.
Methods
Nineteen hemiface transplantations were carried out in 5 groups. Group1, 2- isotransplants were performed between Lewis rats (RT1l) with or without immunosuppression. Hemiface allotransplantations were performed between ACI (RT1a) donors and Lewis (RT1l) recipients. Recipients were treated either with continuous CsA protocol- group 3 or anti-áâTCR/CsA protocol for 7 days– group 4. Short-term immunosuppression was augmented with 4x106 in vivo created donor-recipient chimeric cells (DRCC) - group 5. Evaluation of tolerogenic genes expression levels in skin biopsies (Il-10, Tgfâ, FoxP3) using real-time PCR and flow cytometry analysis of changes in Treg cell population (CD4/25) and chimerism level in blood were performed.
Results
Increased Il-10 and FoxP3 gene expression was observed up to 35 days in allograft group supported by DRCC therapy- group 5 and in group 3 under continuous CsA protocol.
Significantly increased percentage of T regulatory cells in blood at early stage post-transplantation was detected only in group 5.
Conclusion
In DRCC group in face transplant biopsies, up-regulated expression of Il-10 was correlated with expression of FoxP3 and increased amount of Treg cells in blood at day 7 post-transplantation. Immunosuppressive protocol of anti-áâTCR/CsA for 7 days improves chimerism level at early stage post-transplantation. These results might indicate protective effect at early stage post-transplantation of DRCC therapy under 7day immunosuppressive protocol.
