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

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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., Wittenbecher, F., Dziubianau, M., Herholz, A., Mensen, A., Kunkel, D., Blau, O., Blau, I., Thiel, E., Uharek, L., Scheibenbogen, C., 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
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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