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™ 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.
Department of Hematology, Oncology and Tumor Immunology, Charité, Berlin, Germany. il-kang.na@charite.de
Il-Kang
IK
Na
Friedrich
F
Wittenbecher
Mikalai
M
Dziubianau
Anne
A
Herholz
Angela
A
Mensen
Désirée
D
Kunkel
Olga
O
Blau
Igor
I
Blau
Eckhard
E
Thiel
Lutz
L
Uharek
Carmen
C
Scheibenbogen
Kathrin
K
Rieger
Andreas
A
Thiel
D000328:Adult; D000368:Aged; D000818:Animals; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count / Q000379:methods; D002478:Cells, Cultured; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000187:drug effects* / Q000276:immunology*; D014184:Transplantation, Homologous
D000961:Antilymphocyte Serum; C512542:thymoglobulin