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

• Published in: Haematologica (Roma) Vol. 98; no. 1; pp. 23 - 30
• Main Authors: Na, Il-Kang, Wittenbecher, Friedrich, Dziubianau, Mikalai, Herholz, Anne, Mensen, Angela, Kunkel, Désirée, Blau, Olga, Blau, Igor, Thiel, Eckhard, Uharek, Lutz, Scheibenbogen, Carmen, Rieger, Kathrin, Thiel, Andreas
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01.01.2013
• Subjects: Adult; Aged; Animals; Antilymphocyte Serum - adverse effects; Antilymphocyte Serum - therapeutic use; CD4 Lymphocyte Count - methods; Cells, Cultured; Female; Hematopoietic Stem Cell Transplantation - methods; Humans; Male; Middle Aged; Rabbits; T-Lymphocytes - immunology; Thymus Gland - drug effects; Thymus Gland - immunology; Transplantation, Homologous
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2012.067611

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.