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Altered balance between effector T cells and FOXP3+HELIOS+ regulatory T cells after thymoglobulin induction in kidney transplant recipients
Authors:Qizhi Tang  Joey Leung  Kristin Melli  Kimberly Lay  Emmeline L. Chuu  Weihong Liu  Jeffrey A. Bluestone  Sang‐Mo Kang  V. Ram Peddi  Flavio Vincenti
Affiliation:1. Department of Surgery, University of California, San Francisco, CA, USA;2. Diabetes Center, University of California, San Francisco, CA, USA;3. California Pacific Medical Center, San Francisco, CA, USA
Abstract: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.
Keywords:effector T cells  FOXP3  HELIOS  regulatory T cells  renal transplant  thymoglobulin
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