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Rabbit antithymocyte globulin (Thymoglobulin(R)) impairs the thymic output of both conventional and regulatory CD4(+) T cells after allogeneic hematopoietic stem cell transplantation in adult patients

Item Type:Article
Title:Rabbit antithymocyte globulin (Thymoglobulin(R)) impairs the thymic output of both conventional and regulatory CD4(+) T cells after allogeneic hematopoietic stem cell transplantation in adult patients
Creators Name:Na, I.K. and Wittenbecher, F. and Dziubianau, M. and Herholz, A. and Mensen, A. and Kunkel, D. and Blau, O. and Blau, I. and Thiel, E. and Uharek, L. and Scheibenbogen, C. and Rieger, K. and Thiel, A.
Abstract:Rabbit antithymocyte globulin-Genzyme™ is used to prevent graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Common disadvantages of treatment are infectious complications. The effects of rabbit antithymocyte globulin-Genzyme™ on thymic function have not been well-studied. Multicolor flow cytometry was used to analyze the kinetics of conventional and regulatory T cells in adult patients treated (n=12) or not treated (n=8) with rabbit antithymocyte globulin-Genzyme™ during the first 6 months after allogeneic hematopoietic stem cell transplantation. Patients treated with rabbit antithymocyte globulin-Genzyme™ had almost undetectable levels of recent thymic emigrants (CD45RA(+)CD31(+)) of both conventional and regulatory CD4T cells throughout the 6 months after allogeneic hematopoietic stem cell transplantation whereas CD4(+)CD45RA-memory T cells were less affected, but their levels were also significantly lower than in patients not treated with rabbit antithymocyte globulin-Genzyme™. In vitro, rabbit antithymocyte globulin-Genzyme™ induced apoptosis and cytolysis of human thymocytes, and its cytotoxic effects were greater than those of rabbit antithymocyte globulin-Fresenius™. Rabbit antithymocyte globulin-Genzyme™ in combination with a conditioning regimen strongly impairs thymic recovery of both conventional and regulatory CD4(+) T cells. The sustained depletion of conventional and regulatory CD4(+)T cells carries a high risk of both infections and graft-versus-host disease. Our data indicate that patients treated with rabbit antithymocyte globulin-Genzyme™ could benefit from thymus-protective therapies and that trials comparing this product with other rabbit antithymocyte globulin preparations or lymphocyte-depleting compounds would be informative.
Keywords:Antilymphocyte Serum, CD4 Lymphocyte Count, Cultured Cells, Hematopoietic Stem Cell Transplantation, T-Lymphocytes, Thymus Gland, Homologous Transplantation, Animals, Rabbits
Source:Haematologica
ISSN:0390-6078
Publisher:Ferrata Storti Foundation (Italy)
Volume:98
Number:1
Page Range:23-30
Date:January 2013
Official Publication:https://doi.org/10.3324/haematol.2012.067611
PubMed:View item in PubMed

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