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

Abstract

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 CD28(null)CD57(+)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 CD28(null)CD57(+)CD8(+)T cells in anex vivostudy and found that most of them were included in the significant genes onin vitroCCR7(+)CD8(+)T cells. Finally, the decrease of CCR7(+)CD8(+)T cells relative to CD28(null)CD57(+)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.