Costimulatory and Inhibitory T-Cell Receptors; Flow Cytometry; T-Lymphocytes, Regulatory; Translational Medical Research; Transplantation; Transplantation Chimera; Transplantation Immunology; Transplantation Tolerance
- Surgical Research Laboratories
Head: Michael Bergmann
Research Area: The task of the laboratory is to combine molecular/cellular biology and the needs posed by surgical patients. Thus, the laboratory acts at the interface between clinical medicine and basic research, promoting translational medical science.
My main research interest is the role and potency of regulatory T cells (Tregs) in the induction and maintainance of transplantation tolerance.
The establishment of mixed hematopoietic chimerism is an exceptionally potent strategy for the induction of donor-specific tolerance in organ transplantation. We could show that Tregs improve chimerism induction in experimental animal models with reduced intensity conditioning. Moreover, adoptive Treg transfer induced intragraft regulatory mechanisms that prevent chronic rejection.
Currently, I am specifically interested in immunomodulation via interleukin/antibody complexes. By the use of specific IL2/anti-IL2 complexes, which induce selective expansion of Tregs, transplantation tolerance can be achieved.
Techniques, methods & infrastructure
- Mouse models: bone marrow transplantation for the creation of mixed chimeras; murine skin and heterotopic heart transplantation
- Regulatory T cells (in vivo expansion via IL2complexes, in vitro expansion culture, retroviral gene transfer, TGFbeta induction): cell therapy, in-vitro assays
- Multi colour Flow-cytometry (Canto II, Fortessa LSR): Immune monitoring, Leucocyte subset analysis, Flow-crossmatch
- Mechanisms of IL-2 induced transplantation tolerance (2018)
Source of Funding: FWF (Austrian Science Fund), stand-alone project
- IL-2 cytokine/antibody mediated transplantation tolerance (2014)
Source of Funding: FWF (Austrian Science Fund), Ewin Schrödinger Fellowship
- Pilat, N. et al., 2016. Incomplete clonal deletion as prerequisite for tissue-specific minor antigen tolerization. JCI Insight, 1(7). Available at: http://dx.doi.org/10.1172/jci.insight.85911.
- Pilat, N. et al., 2015. Rapamycin and CTLA4Ig Synergize to Induce Stable Mixed Chimerism Without the Need for CD40 Blockade. American Journal of Transplantation, 15(6), pp.1568-1579. Available at: http://dx.doi.org/10.1111/ajt.13154.
- Pilat, N. et al., 2014. T-regulatory cell treatment prevents chronic rejection of heart allografts in a murine mixed chimerism model. The Journal of Heart and Lung Transplantation, 33(4), pp.429-437. Available at: http://dx.doi.org/10.1016/j.healun.2013.11.004.
- Pilat, N. & Wekerle, T., 2010. Transplantation tolerance through mixed chimerism. Nature Reviews Nephrology, 6(10), pp.594-605. Available at: http://dx.doi.org/10.1038/nrneph.2010.110.
- Pilat, N. et al., 2010. Treg-Therapy Allows Mixed Chimerism and Transplantation Tolerance Without Cytoreductive Conditioning. American Journal of Transplantation, 10(4), pp.751-762. Available at: http://dx.doi.org/10.1111/j.1600-6143.2010.03018.x.