Kidney Transplant Outcome Is Associated with Regulatory T Cell Population and Gene Expression Early after Transplantation

Abstract

Successful long-term kidney allograft survival with parallel reduction of complications resulting from prolonged immunosuppressive treatment is a goal in kidney transplantation. We studied the immune changes in cell phenotypes and gene expression induced by kidney transplantation. Our goal was to find a phenotypic and/or transcriptional pattern that might be considered prognostic for the kidney transplant outcome. The analysis was performed prospectively on 36 KTx recipients sampled during the first year and followed for five years after transplantation and on 40 long-term KTx recipients (7.9 ± 2.2 y. post-KTx). The research involved flow cytometry assessment of lymphocyte subpopulations (including Tregs and CD3+CD8+CD28− lymphocytes) and gene expression analysis of immune-related genes (CD4, CD8, CTLA4, GZMB, FOXP3, IL10, IL4, ILR2A, NOTCH, PDCD1, PRF1, TGFB, and TNFA). The analysis of patterns observed over the first post-KTx year was confronted with control, pretransplant, and long-term transplant results. Treg counts at months one and three post-KTx correlated positively with the current and future allograft function. FOXP3 gene expression at month one post-KTx was also associated with long-term allograft function. The KTx-induced CD3+CD8+CD28− population correlated with GZMB and PRF1 expression and suggested their cytotoxic properties. The size of the Treg population and regulatory FOXP3 gene expression in the early period after transplantation are associated with kidney transplant outcome. The outlined predictive power of the Treg population needs to be investigated further to be confirmed as one of the immune monitoring strategies that may help achieve the best long-term kidney allograft outcomes.

CD62L Percentage in Peripheral T Cells of Kidney Transplant Recipients Children

“…Unlike our findings; Krajewska, et al showed a negative correlation between the recipient age and Treg population following KT [1]. Donor/recipient age mismatch in our study is an inevitable confounding factor, since our pediatric population received only adult living renal graft based on national regulations.…”

“…Recipient's immune status/sensitization, quality of organ, and immunosuppressive treatment are some of the factors that determine graft function and survival after Kidney Transplantation (KT) [1]. Different strategies have been developed in a trial to induce graft tolerance that necessitate better understanding of basic tolerogenic mechanisms as well as the capital role that T cells play during transplant rejection [2].…”

Monitoring of B Cell in Kidney Transplantation: Development of a Novel Clusters Analysis and Role of Transitional B Cells in Transplant Outcome

“…Therefore, we do not know what happens in the first days after treatment. This limitation also applies to other studies [ 34 ], where the first sample had a month after treatment. It is likely that the effect of thymoglobulin is only observable in the short term and that the subsequent homeostatic lymphoproliferation of BL makes it difficult to detect differences in samples collected several months after drug administration.…”

“…Our data show that RTRs receiving thymoglobulin have a PTX reduction in the frequency of naive BL associated with a relative increase in memory BL levels; however, when comparing BL levels between RTR with and without thymoglobulin, we did not obtain statistically significant differences. Although Zand et al [ 11 ] showed the in vitro anti-B effect of thymoglobulin by activating apoptotic pathways, several studies suggest a small in vivo effect on BL, even at high concentrations [ 34 ]. Gurkan et al [ 35 ] observed no differences in the absolute levels of BL of RTR treated with thymoglobulin.…”

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

“…[1] Indeed, markers for the activation of CD8 + T cells can be detected in the peripheral blood isolated from kidney-transplant recipients (KTRs); especially, CD8 + T cell subsets belonging to the terminally-differentiated effector-cell state are known to be involved in the process of allograft rejection. [2][3][4][5] In contrast, CD8 + T cell subtypes that display a naïve cell state can be involved in an "anti-rejection" process by regulation of effector T cells. [6][7][8] Therefore, it is possible that the dynamics of CD8 + T subsets in the peripheral blood can show a significant change according to "rejection" and "stable" state; hence it has been proposed that monitoring of CD8 + T cells subsets may be useful for detecting acute allograft rejection.…”