We investigated the phenotype and molecular signatures of CD8+ T cell subsets in kidney-transplant recipients (KTRs) with biopsy-proven T cell-mediated rejection (TCMR). We included 121 KTRs and divided them into three groups according to the pathologic or clinical diagnosis: Normal biopsy control (NC)(n = 32), TCMR (n = 50), and long-term graft survival (LTGS)(n = 39). We used flowcytometry and microarray to analyze the phenotype and molecular signatures of CD8+ T cell subsets using peripheral blood from those patients and analyzed significant gene expressions according to CD8+ T cell subsets. We investigated whether the analysis of CD8+ T cell subsets is useful for predicting the development of TCMR. CCR7+CD8+ T cells significantly decreased, but CD28nullCD57+CD8+ T cells and CCR7-CD45RA+CD8+ T cells showed an increase in the TCMR group compared to other groups (p<0.05 for each); hence CCR7+CD8+ T cells showed significant negative correlations to both effector CD8+ T cells. We identified genes significantly associated with the change of CCR7+CD8+ T, CCR7-CD45RA+CD8+ T, and CD28nullCD57+CD8+ T cells in an ex vivo study and found that most of them were included in the significant genes on in vitro CCR7+CD8+ T cells. Finally, the decrease of CCR7+CD8+ T cells relative to CD28nullCD57+ T or CCR7-CD45RA+CD8+ T cells can predict TCMR significantly in the whole clinical cohort. In conclusion, phenotype and molecular signature of CD8+ T subsets showed a significant relationship to the development of TCMR; hence monitoring of CD8+ T cell subsets may be a useful for predicting TCMR in KTRs.
Bibliographical noteFunding Information:
BH Chung, CD Kim, and SH Lee received a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI13C1232) and EJ Ko received a grant from the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (2018M3A9E802151). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Copyright: © 2020 Ko et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ASJC Scopus subject areas