PLoS ONE (Jan 2020)

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

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

DOI
https://doi.org/10.1371/journal.pone.0234323
Journal volume & issue
Vol. 15, no. 6
p. e0234323

Abstract

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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.