Overview
In this study, the investigators will establish a workflow to generate unique patterns of the donor-reactive T cell repertoire using mixed lymphocyte reactions to select alloreactive T cell clones prior to transplantation Tissue infiltrating as well as blood bound T cells will be characterized based on:
- Identification of donor-specific T cell receptor sequences pre- and post-transplant by in vitro expansion to determine unique patterns
- Quantification and comparison of donor-specific T cell clones in kidney biopsy and blood samples.
- Analysis of the TCR repertoire diversities derived from kidney biopsy and blood samples and association of repertoire diversities with the histomorphological phenotype of T cell mediated rejection.
- Identification of T cell subtypes within the donor-reactive population. The investigators specifically hypothesize that highly expanded donor-reactive T cell clones in both kidney tissue and blood samples at time of indication biopsy are associated with the histological phenotype of acute T cell mediated rejection. The investigators have previously shown that there is a strong correlation between highly expanded tissue-resident T cell clones and the repertoire found in periphery blood samples. To trace and quantify donor reactive T cells the investigators will apply a truly quantitative approach for immune repertoire profiling based on high- throughput sequencing. The investigators ultimate goal is to develop a diagnostic tool to assess alloreactive cellular immunoresponses based on peripheral blood samples.
Description
Kidney transplant recipients receiving a non lymphodepletional induction therapy at the investigators center will be included in this study.
Alloreactive T cells are defined prior to transplantation via a mixed lymphocyte reaction of donor and recipient PBMC's.
Following transplantation PBMC's will be sampled at management (3 and 12 months) and for-cause biopsies and fifteen patients with histological proven acute T cell mediated rejection will be compared to 15 patients without histopathological signs of alloimmune response in time matched for-cause biopsies.
T cell receptor beta chains of T cells found in the circulation and the allograft biopsy will be sequenced via Next generation sequencing.
Abundance of alloreactive T cells of the overall repertoire pre-and post-transplant and their presence in the allograft will be assessed.
The diversity of the overall repertoire and alloreactive repertoire will be compared between these two groups.
Eligibility
Inclusion Criteria:
- Kidney transplantation in our center
Exclusion Criteria:
- Donor not evaluated by our center