Quantitative analysis of regulatory T cells in kidney graft recipients: A relationship with calcineurin inhibitor level

Human CD8(+)CD28(-) T suppressor cells were previously shown to be involved in the control of the immune response to transplanted allografts. It seems essential to examine how immunosuppressive drugs influence these cells. However, the CD8(+)CD28(-) population contains both suppressor (Ts) and cytotoxic (Tc) T cells, and the phenotype of the Ts subpopulation has not been identified explicitly. It is proposed that the transcription factor FOXP3 may be helpful in distinguishing the Ts and Tc subpopulations. The aim of this study was to evaluate the influence of the immunosuppressive drugs cyclosporine A (CsA) and rapamycin (RAPA) on the level, suppressor properties, and phenotype of human CD8(+)CD28(-) T cells in vitro. The model used was the mixed leukocyte reaction performed with peripheral blood mononuclear cells from healthy volunteers. It was observed that CD8(+)CD28(-) T cells from cultures with CsA or RAPA had similar suppressor properties to cells from control cultures, although the drugs influenced the expression of FOXP3. CsA and RAPA did not interfere with the suppressor properties of human CD8(+)CD28(-) T cells in vitro, although they affected the expression of the FOXP3 molecule.

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“…CD28 -lymphocytes, which may correspond to T suppressor or cytotoxic cells (Calvo-Turrubiartes et al 2009). …”

Section: Discussionmentioning

confidence: 99%

Suppressor Properties of Human CD8+CD28− T Cells in Mixed Leukocyte Reaction are not Affected by CsA and RAPA

Korecka-Polak

Bocian

Pachówka

et al. 2016

Arch. Immunol. Ther. Exp.

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“…However, long-term treatment with CNIs is associated with complications such as nephrotoxicity, diabetes mellitus and secondary malignancies. [3][4][5] Additionally, CNIs induce undesirable changes in the immune response after kidney transplantation, including a reduction in the proportion and function of CD4 + regulatory T cells (CD4 + Treg cells) within the peripheral blood mononuclear cell (PBMC) population, [6][7][8] and an up-regulation of T helper type 17 (Th17) cell-associated pathways, which are involved in allograft rejection. [9][10][11][12][13][14][15][16][17] Hence, CNI-based immunosuppression may in fact contribute to the progression of chronic allograft dysfunction in kidney transplant recipients (KTRs).…”

Section: Introductionmentioning

confidence: 99%

The effect of mammalian target of rapamycin inhibition on T helper type 17 and regulatory T cell differentiation in vitro and in vivo in kidney transplant recipients

et al. 2014

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SummarySirolimus (SRL) is a promising alternative to calcineurin inhibitors, such as tacrolimus (TAC), in kidney transplant recipients (KTRs), but the immunological benefits of conversion from calcineurin inhibitors to SRL are not fully investigated. In the present study, we evaluated the effect of conversion from TAC to SRL on the T helper type 17/regulatory T (Th17/Treg) axis in three separate studies. First, the effect of SRL on the Th17/Treg axis was evaluated in vitro using peripheral blood mononuclear cells (PBMCs). Second, the effect of conversion from TAC to SRL on the Th17/Treg axis was studied in KTRs. Finally, the effect of SRL on CD8

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“…After kidney transplantation, alloimmune responses by CD4+ T cell activation mediate most cases of allograft rejection [1]. Therefore, most immune suppressants have been developed to downregulate the activation and differentiation of effector CD4+ T cells to prevent the generation of these alloimmune responses [2], [3].…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of Th17 Cells during the Early Post-Transplant Period in Patients under Calcineurin Inhibitor Based Immunosuppression

Chung

Kim

et al. 2012

PLoS ONE

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Accumulating evidence suggests that Th17 cells play a role in the development of chronic allograft injury in transplantation of various organs. However, the influence of current immunosuppressants on Th17-associated immune responses has not been fully investigated. We prospectively investigated the changes in Th17 cells in peripheral blood mononuclear cells (PBMCs) collected before and 1 and 3 months after KT in 26 patients and we investigated the suppressive effect of tacrolimus on Th17 in vitro. In the early posttransplant period, the percentage of Th17 cells and the proportion of IL-17-producing cells in the effector memory T cells (TEM) were significantly increased at 3 months after transplantation compared with before transplantation (P<0.05), whereas Th1/Th2 cells and TEM cells were significantly decreased. The degree of increase in Th17 during the early posttransplant period was significantly associated with allograft function at 1 year after transplantation (r = 0.4, P<0.05). In vitro, tacrolimus suppressed Th1 and Th2 cells in a concentration-dependent manner, but did not suppress Th17 cells even at high concentration. This suggests that current immunosuppression based on tacrolimus is inadequate to suppress Th17 cells in KTRs, and dysregulation of Th17 may be associated with the progression of CAD.

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Quantitative analysis of regulatory T cells in kidney graft recipients: A relationship with calcineurin inhibitor level

Cited by 33 publications

References 34 publications

Suppressor Properties of Human CD8+CD28− T Cells in Mixed Leukocyte Reaction are not Affected by CsA and RAPA

Suppressor Properties of Human CD8+CD28− T Cells in Mixed Leukocyte Reaction are not Affected by CsA and RAPA

The effect of mammalian target of rapamycin inhibition on T helper type 17 and regulatory T cell differentiation in vitro and in vivo in kidney transplant recipients

Dysregulation of Th17 Cells during the Early Post-Transplant Period in Patients under Calcineurin Inhibitor Based Immunosuppression

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