Phenotype and molecular signature of CD8 T cell subsets in T cell- mediated rejections after kidney transplantation.

Ko, Eun Jeong; Seo, Jung-Woo; Kim, Kyoung Woon; Kim, Bo-Mi; Cho, Jang-Hee; Kim, Chan-Duck; Seok, Junhee; Yang, Chul Woo; Lee, Sang-Ho; Chung, Byung Ha

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 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.

KIDNEY transplantation; PHENOTYPES; GENE expression

PLoS ONE, 2020, Vol 15, Issue 6, p1

1932-6203

Academic Journal

10.1371/journal.pone.0234323