Altered balance between effector T cells and FOXP3⁺HELIOS⁺regulatory T cells after thymoglobulin induction in kidney transplant recipients

Abstract

Summary This study examined the effect of thymoglobulin induction therapy on leukocyte population dynamics in kidney transplant patients. Patients receiving standard immunosuppression were compared with those who received additional thymoglobulin at the time of kidney transplantation. Thymoglobulin induction led to an immediate and significant decrease of all T cells and NK cells, but not B cells or monocytes. CD8+ T cells recovered to near pretransplant level by 4 weeks post‐transplant. CD4+ T cells remained at less than 30% of pretransplant level for the entire study period of 78 weeks. Both CD4+ and CD8+ T cells showed reduced cytokine production after recovery. Deletion of CD4+FOXP3+HELIOS+ regulatory T cells (Tregs) was less profound than that of CD4+FOXP3− cells, thus the relative percentage of Tregs elevated significantly when compared with pretransplant levels in thymoglobulin‐treated patients. In contrast, the percentages of Tregs and their expression of FOXP3 in the standard immunosuppression group decreased steadily and by 12 weeks after transplant the average percentage of Tregs was 56% of the pretransplant level. Thus, thymoglobulin‐induced deletion of T cells led to significant and long‐lasting alterations of the T‐cell compartment characterized by a preservation of Tregs and long‐lasting reduction in CD4+, and potentially pathogenic, T cells.

Differential depletion of total T cells and regulatory T cells and prolonged allotransplant survival in CD3Ɛ humanized mice treated with polyclonal anti human thymocyte globulin

“…This is in line with earlier studies showing that anti-CD3 mAbs may induce Helios expression in Tregs, and that the Helios + Tregs produce less IFN-γ and IL2 [27]. Interestingly, it has been shown in kidney transplant recipients receiving ATG at the time of transplantation that depletion of CD4 + Helios + Foxp3 + T cells was less pronounced compared to CD4 + Foxp3 - T cells [28]. In kidney transplant patients, Bouvy et al found [29] an increase of the percentages of Tregs 6 months following ATG treatment in comparison with Basiliximab (anti-CD25 antibody) therapy.…”

Impact of Immune-Modulatory Drugs on Regulatory T Cell

“…ATG induction therapy in vivo reduces the absolute number of Treg, but less than that for Tconvs, favorably altering the Treg/Tconv ratio 29,32,33 . Furthermore, Treg recover faster during immune reconstitution following ATG treatment, contributing to the sustained elevation of Treg/Tconv ratio 34 .…”

Peripheral and Thymic Foxp3+ Regulatory T Cells in Search of Origin, Distinction, and Function

“…Elkord et al observed that there was an increased frequency of Helios + Tregs in the peripheral blood of patients with renal cell carcinoma, particularly after IL2 treatment (27). Another study revealed that there was a selective preservation of the Helios + Tregs in kidney transplant recipients that received thymoglobulin induction and a reduction in control patients (28). Similarly, others have noted an expansion of Helios + Tregs in patients with active systemic lupus erythematosus (29).…”