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NGS assessment of donor reactive T cell repertoire

Following the introduction of highly potent immunosuppressive regimens in combination with induction therapy, a significant reduction of acute rejection episodes and an improvement in short term graft survival have been achieved. However, a small number of transplanted organs continue to be lost following an acute rejection (AREJ) episode, but long-term graft function and survival following this kind of immunological injury poses even greater problems to patient management.

Two principal histologic forms of acute rejection are distinguished: a) acute cellular rejection (T-cell mediated) and b) acute anti-body mediated rejection. Cellular rejection with CD8+ and CD4+ T lymphocytes plays a central role and accounts for the larger fraction of acute rejection episodes. Lymphocyte infiltrates in the kidney are the hallmark of T-cell mediated rejection. T cells require at least two signals: The first is delivered when the T cell receptor (TCR) binds to the MHC-allopeptide complex on APCs. The second signal termed “costimulation” involves ligation of specific molecules on the surface of T cells to molecules on APCs, e.g. CD28 binds CD80 and CD86 molecules on APCs fostering the cellular immune response. In this regard, the nature of the lymphoid cells that infiltrate the transplanted kidney is of special interest. Little is known about the molecular nature of these infiltrates, particularly as it relates to the T-cell receptor (TCR) repertoire.


Head

Prof.(FH) DI Dr. Stephan M. Winkler

Researchers

Susanne Schaller, MMSc

Prof.(FH) DI Dr. Stephan M. Winkler

Julia Vetter

Duration

10/2017 - present

Research Areas

Immunology

Data Mining

Research Institutions

University of Applied Sciences, Upper Austria, Hagenberg Campus

Medical University of Vienna

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Finished Projects

NGS assessment of donor reactive T cell repertoire

Following the introduction of highly potent immunosuppressive regimens in combination with induction therapy, a significant reduction of acute rejection episodes and an improvement in short term graft survival have been achieved. However, a small number of transplanted organs continue to be lost following an acute rejection (AREJ) episode, but long-term graft function and survival following this kind of immunological injury poses even greater problems to patient management.

Two principal histologic forms of acute rejection are distinguished: a) acute cellular rejection (T-cell mediated) and b) acute anti-body mediated rejection. Cellular rejection with CD8+ and CD4+ T lymphocytes plays a central role and accounts for the larger fraction of acute rejection episodes. Lymphocyte infiltrates in the kidney are the hallmark of T-cell mediated rejection. T cells require at least two signals: The first is delivered when the T cell receptor (TCR) binds to the MHC-allopeptide complex on APCs. The second signal termed “costimulation” involves ligation of specific molecules on the surface of T cells to molecules on APCs, e.g. CD28 binds CD80 and CD86 molecules on APCs fostering the cellular immune response. In this regard, the nature of the lymphoid cells that infiltrate the transplanted kidney is of special interest. Little is known about the molecular nature of these infiltrates, particularly as it relates to the T-cell receptor (TCR) repertoire.


Head

Prof.(FH) DI Dr. Stephan M. Winkler

Researchers

Susanne Schaller, MMSc

Prof.(FH) DI Dr. Stephan M. Winkler

Julia Vetter

Duration

10/2017 - present

Research Areas

Immunology

Data Mining

Research Institutions

University of Applied Sciences, Upper Austria, Hagenberg Campus

Medical University of Vienna

Back to Projects