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.

Rabbit antithymocyte globulin-Genzyme (TM) 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 (TM) 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 (TM) during the first 6 months after allogeneic hematopoietic stem cell transplantation. Patients treated with rabbit antithymocyte globulin-Genzyme (TM) had almost undetectable levels of recent thymic emigrants (CD45RA(+) CD31(+)) of both conventional and regulatory CD4 T 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 (TM). In vitro, rabbit antithymocyte globulin-Genzyme (TM) induced apoptosis and cytolysis of human thymocytes, and its cytotoxic effects were greater than those of rabbit antithymocyte globulin-Fresenius (TM). Rabbit antithymocyte globulin-Genzyme (TM) 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 (TM) 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. (C) 2013 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2012.067611