Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 18, Issue 1, Pages 63-73Publisher
WILEY
DOI: 10.1111/ajt.14410
Keywords
basic (laboratory) research; science; kidney transplantation; nephrology; natural killer (NK) cells; NK receptors; rejection: antibody-mediated (ABMR); rejection; T cell biology; microarray; gene array
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Funding
- Roche Organ Transplant Research Foundation
- University Hospital Foundation at the University of Alberta
- Industrial Research Assistance Program
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Human organ allograft rejection depends on effector lymphocytes: NK cells in antibody-mediated rejection (ABMR) and effector T cells in T cell-mediated rejection (TCMR). We hypothesized that NK cell CD16a stimulation and CD8 T cell TCR/CD3 stimulation represent highly similar effector systems, and should lead to shared molecular changes between ABMR and TCMR. We studied similarity between soluble proteins and the transcripts induced in CD16a stimulated NK cells and TCR/CD3-stimulated T cells in vitro. Of 30 soluble mediators tested, CD16a-activated NK cells and CD3/TCR activated T cells produced the same limited set of five mediatorsCCL3, CCL4, CSF2, IFNG, and TNF and failed to produce 25 others. Many transcripts increased in stimulated NK cells were also increased in CD3-stimulated CD8 T cells (FDR < 0.05), including IFNG, CSF2, CCL3, CCL4, and XCL1. We hypothesized that shared transcripts not produced by other cell types should be expressed both in ABMR and TCMR kidney transplant biopsies. CD160, XCL1, TNFRSF9, and IFNG were selective for TCR/CD3-activated T cells and CD16a-NK cells and all were strongly increased in ABMR and TCMR. The molecules such as CD160 and XCL1 shared between NK cells in ABMR and effector T cells in TCMR may hold insights into important rejection mechanisms.
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