Influence Of Steroid Exposure On CMV Specific T Cells Following Allogeneic Stem Cell Transplantation

• Published in: Blood 2013-11, Vol.122 (21), p.5488-5488
• Main Authors: Link, Cornelia S., Rücker-Braun, Elke, Tuve, Sebastian, Matko, Sarah, Schmitz, Marc, Wehner, Rebekka, Tunger, Antje, Sockel, Katja, Parmentier, Stefani, Middeke, Jan Moritz, Boldt, Änne, Schetelig, Johannes, Odendahl, Markus, Tonn, Torsten, Bornhäuser, Martin, Heidenreich, Falk
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V122.21.5488.5488

CMV-infection is a serious complication in patients after allogeneic stem cell transplantation (SCT) where immunosuppressive therapy and impaired T cell reconstitution result in a high risk for viral infections. Monitoring of CMV-virus load by PCR and preemptive therapy are important tools to prevent CMV disease. However, CMV specific cytotoxic T cells (CMV-CTLs) are needed to successfully control CMV-infections. CMV-specific multimers composed of the patients HLA Class I molecule bound to CMV pp65 epitopes give the possibility to monitor CMV-CTLs. Here, we present the case of CMV-reactivation following SCT for AML. The percentage of CMV-specific CD8+ T cells was determined by flow cytometry and mapped to clinical and laboratory parameters of the patient. CD8+ T cells were detected using CD8-fluorescein isothiocyanate (FITC, Beckman Coulter) antibody and CD3 as a T-cell marker was labeled with CD3-allophycocyanin (APC, MACS Miltenyi Biotec) antibody. CMV-specific CD8+ T cells were detected using the CMV major histocompatibility complex (MHC) with Strep-Tactinphycoerythrin (PE) conjugate (Streptamers, IBA GmbH). A 60 years old male patient was diagnosed with acute myeloid leukemia (AML) with 95% myeloid blasts in the bone marrow and extramedullary AML manifestations at the time of diagnosis. Following induction therapy the patient was transplanted from a matched unrelated donor. The stem cell recipient as well as his donor had been tested sero-positive for CMV prior to SCT. Within the first month following transplantation, the patient developed an effective CMV specific immunity as seen by high levels of CMV-specific T cells (Figure 1). About three months following transplantation the patient was diagnosed with intestinal GVHD requiring high-dose glucocorticoid treatment. Following steroid exposure, levels of CMV-CTLs dropped and shortly thereafter rising CMV-copy numbers were observed which was accompanied by clinical signs of CMV enteritis. With the administration of antiviral treatment the CMV specific virus load decreased. However, levels of CMV-CTLs remained low, presumably as a result of ongoing steroid exposure. High levels of CMV-CTLs appeared to control CMV, as seen by a non-detectable virus load in standard PCR testing. The close correlation between the drop in CMV-CTL count and CMV activation highlights the potential of this method to monitor and understand immune responses to CMV following SCT. Of note, early presence of high frequencies of CMV-