Altered balance between effector T cells and FOXP3+HELIOS+ regulatory T cells after thymoglobulin induction in kidney transplant recipients
Qizhi Tang
Department of Surgery, University of California, San Francisco, CA, USA
Search for more papers by this authorJoey Leung
Department of Surgery, University of California, San Francisco, CA, USA
Search for more papers by this authorKristin Melli
Department of Surgery, University of California, San Francisco, CA, USA
Search for more papers by this authorKimberly Lay
Department of Surgery, University of California, San Francisco, CA, USA
Search for more papers by this authorEmmeline L. Chuu
Department of Surgery, University of California, San Francisco, CA, USA
Search for more papers by this authorWeihong Liu
Diabetes Center, University of California, San Francisco, CA, USA
Search for more papers by this authorJeffrey A. Bluestone
Diabetes Center, University of California, San Francisco, CA, USA
Search for more papers by this authorSang-Mo Kang
Department of Surgery, University of California, San Francisco, CA, USA
Search for more papers by this authorV. Ram Peddi
California Pacific Medical Center, San Francisco, CA, USA
Search for more papers by this authorFlavio Vincenti
Department of Surgery, University of California, San Francisco, CA, USA
Search for more papers by this authorQizhi Tang
Department of Surgery, University of California, San Francisco, CA, USA
Search for more papers by this authorJoey Leung
Department of Surgery, University of California, San Francisco, CA, USA
Search for more papers by this authorKristin Melli
Department of Surgery, University of California, San Francisco, CA, USA
Search for more papers by this authorKimberly Lay
Department of Surgery, University of California, San Francisco, CA, USA
Search for more papers by this authorEmmeline L. Chuu
Department of Surgery, University of California, San Francisco, CA, USA
Search for more papers by this authorWeihong Liu
Diabetes Center, University of California, San Francisco, CA, USA
Search for more papers by this authorJeffrey A. Bluestone
Diabetes Center, University of California, San Francisco, CA, USA
Search for more papers by this authorSang-Mo Kang
Department of Surgery, University of California, San Francisco, CA, USA
Search for more papers by this authorV. Ram Peddi
California Pacific Medical Center, San Francisco, CA, USA
Search for more papers by this authorFlavio Vincenti
Department of Surgery, University of California, San Francisco, CA, USA
Search for more papers by this authorConflicts of Interest: All authors declare no conflict of interest.
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.
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