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

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^nullCD57⁺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^nullCD57⁺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 CD28^nullCD57⁺ 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.