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In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
Published on: August 12, 2017
Interpreting NK cell transcripts versus T cell transcripts in renal transplant biopsies.
L G Hidalgo1, J Sellares, B Sis
1Department of Laboratory Medicine and Pathology, Division of Nephrology and Transplant Immunology, University of Alberta, Edmonton, Alberta, Canada.
Summary
Natural killer (NK) cell transcripts indicate antibody-mediated rejection in late kidney transplants. However, NK or T cells expressing NK transcripts also play roles in T cell-mediated rejection and inflammation from injury.
Area of Science:
- Transplant immunology
- Cellular immunology
- Molecular diagnostics
Background:
- Distinguishing natural killer (NK) and T cell involvement in kidney transplant rejection is challenging due to overlapping cellular features and transcript markers.
- Accurate assessment of NK versus T cell transcript burdens is crucial for understanding rejection mechanisms and guiding treatment.
Purpose of the Study:
- To develop and apply methods for separately quantifying NK cell and T cell transcript burdens in kidney transplant biopsies.
- To investigate the distinct roles of NK cells and T cells in different types of kidney transplant rejection and inflammation.
Main Methods:
- Defined non-overlapping gene sets specific for NK cells (4 transcripts) and T cells (5 transcripts).
- Analyzed NK- versus T cell transcript expression using microarrays in 403 kidney transplant biopsies (182 early, 221 late).
- Correlated transcript burdens with clinical and histological findings, including rejection type, inflammation, and donor-specific antibodies (DSA).
Main Results:
- High NK-cell transcript expression correlated with antibody-mediated rejection (AMR) in late biopsies, associated with microvascular inflammation and DSA.
- In early biopsies, T cell-mediated rejection (TCMR) showed high NK-cell and T cell transcripts, correlating with interstitial inflammation and tubulitis, without DSA.
- Both NK-cell and T cell transcripts were moderately increased in kidneys with inflammation secondary to injury or atrophy scarring.
Conclusions:
- NK cells play a distinct role in late AMR, identified by specific transcript signatures.
- NK-transcript expressing cells, potentially including T cells with NK features, are involved in TCMR and inflammation related to injury or scarring.
- Separate quantification of NK and T cell transcripts aids in differentiating rejection pathways and understanding inflammatory processes in kidney allografts.
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