Brief communication Rabbit antithymocyte globulin induces rapid expansion of effector memory CD8 T cells without accelerating acute graft versus host disease $ Friedrich Wittenbecher a , Kathrin Rieger a , Mikalai Dziubianau d , Anne Herholz b , Angela Mensen e , Igor Wolfgang Blau a , Lutz Uharek a , Bernd Dörken a,f , Andreas Thiel c , Il-Kang Na a,e,f,n a Department of Hematology, Oncology and Tumor Immunology, Charité, Berlin, Germany b Department of Medicine, Division of Gastroenterology, Infectiology and Rheumatology, Charité, Berlin, Germany c Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité CVK, Berlin, Germany d Renal and Transplant Research Unit, Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité CVK, Berlin, Germany e Institute of Medical Immunology, Charité CVK, Berlin, Germany f Experimental and Clinical Research Center (ECRC), Berlin, Germany article info Article history: Received 8 June 2013 Received in revised form 24 July 2013 Accepted 15 September 2013 Available online 27 September 2013 Keywords: HSCT antithymocyte globulin CD8 T cell effector memory naive abstract Rabbit antithymocyte globulin (Thymoglobulin s ) is commonly used as graft-versus-host disease (GvHD) prophylaxis. Since we found similar total CD8 T cell numbers in patients with and without Thymoglo- bulin s therapy within the first six months after allogeneic hematopoietic stem cell transplantation, we have analyzed the reconstitution of the CD8 T cell compartment in detail. After T cell-depletion, higher and more sustained proliferative capacity of memory CD8 T cells resulted in their rapid expansion, whereas the fraction of naive CD8 T cells decreased. Importantly, this shift towards effector memory CD8 T cells did not accelerate the incidence of GvHD. & 2013 The Authors. Published by Elsevier Ltd. All rights reserved. 1. Introduction One of the major complications associated with allogeneic hematopoietic stem cell transplantation (alloHSCT) is the high incidence of acute graft-versus-host disease (GvHD) caused by donor T-lymphocytes. Depletion of donor T-lymphocytes is a well- established therapeutic option for GvHD-prophylaxis. Recently, we showed a sustained depletion of conventional and regulatory CD4 T cells in patients treated with ATG-Genzyme ™ (Thymoglobulin s , ATG-G) [1], a polyclonal antibody preparation containing a broad spectrum of antibodies directed against T cells [2] and potentially thymic stromal cells. Interestingly, total CD8 T cell counts were similar in ATG-G treated and untreated patients[1]. In principle, T cell recovery after transplantation can take place through thymus dependent regeneration as well as by proliferation of existing T cells [3]. Here, we addressed whether the rapid CD8 T cell recovery after ATG-G depletion resulted from accelerated CD8 T cell regeneration or increased peripheral CD8 T cell proliferation and in how far this influenced GvHD incidence. Therefore, we studied the distribution of different CD8 T cell subsets and their proliferative capacity in ATG-G treated patients of the same patient cohort. 2. Material and methods A detailed description of methods and patient cohorts can be found in Na et al. [1] (approval by the Charité – Berlin local ethics committee no. EA4/128/09). Briefly, we compared CD8 T cell reconstitution in 12 alloHSCT patients receiving ATG-G according to standard procedure protocols (ATG-G group, for d þ 180: n ¼ 11) with 8 alloHSCT patients not receiving ATG-G (noATG-G group, for d þ 180: n ¼ 3). Patient characteristics and clinical outcome are Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/lrr Leukemia Research Reports 2213-0489/$ - see front matter & 2013 The Authors. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.lrr.2013.09.001 ☆ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which per- mits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. n Corresponding author at: Charité – Campus Virchow-Klinikum, Hämatologie, Onkologie und Tumorimmunologie Augustenburger Platz 113353 Berlin, Germany. Tel.: þ49 30450553111; fax: þ49 30450553914. E-mail address: il-kang.na@charite.de (I.-K. Na). Leukemia Research Reports 2 (2013) 82–85