Document Detail


Quantitative analysis of EBV-specific CD4/CD8 T cell numbers, absolute CD4/CD8 T cell numbers and EBV load in solid organ transplant recipients with PLTD.
MedLine Citation:
PMID:  17331848     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Post transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients is assumed to be the result of impaired Epstein-Barr Virus (EBV)-specific cellular immunity. We analyzed the absolute CD4 and CD8 T cell counts as well as the EBV-specific CD4 and CD8 T cell responses in relation to EBV load in SOT recipients with PTLD. A prospective, single center study was initiated and 10 immunosuppressed patients with diagnosis of PTLD were analyzed and compared to 3 patients without PTLD (2 SOT recipients with EBV-reactivation, 1 patient with Infectious Mononucleosis) and 6 healthy EBV positive controls. EBV-specific CD8 T cells were enumerated using HLA class I tetramers and the IFN-gamma cytokine secretion assay. EBNA1-specific CD4 T cells were analyzed after protein stimulation and EBV load was quantified by real-time PCR. Absolute CD8 T cell counts were highly variable in all 19 cases analyzed. In contrast, the absolute EBV-specific CD8 T cell count was found to be low in 7/9 patients with PTLD (<5/microl whole blood). These frequencies were similar to absolute EBV-specific CD8 T cell numbers observed in healthy EBV positive donors, but much lower compared to patients with EBV reactivation but no PTLD. Absolute CD4 T cell counts were significantly lower in PTLD patients (mean: 336/microl+/-161 vs. controls 1008/microl+/-424, p=0.0001), with EBNA1-specific CD4 T cell responses being also low, but highly variable. Moreover, low absolute CD4 T cell counts (<230/microl) were associated with an elevated EBV load (>1000 copies/microg DNA). We conclude that SOT recipients with PTLD have an inadequate functional EBV-specific T cell response. Our data suggest that the frequency and function of circulating EBV-specific CD8 T cells are dependent on absolute CD4 T cell counts. Further studies are needed to verify if a low absolute CD4 T cell count presents a risk factor for the development of PTLD in SOT recipients.
Authors:
Kathrin Sebelin-Wulf; Tuan D Nguyen; Stephan Oertel; Matthias Papp-Vary; Ralf Ulrich Trappe; Antje Schulzki; Antonio Pezzutto; Hanno Riess; Marion Subklewe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-11-29
Journal Detail:
Title:  Transplant immunology     Volume:  17     ISSN:  0966-3274     ISO Abbreviation:  Transpl. Immunol.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-02     Completed Date:  2007-05-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9309923     Medline TA:  Transpl Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  203-10     Citation Subset:  IM    
Affiliation:
Charité-Universitaetsmedizin Berlin, Campus Virchow Klinikum, Med. Klinik m. S. Haematologie/Onkologie, D-13353 Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
CD4-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / immunology*
Cell Count
Child
Epstein-Barr Virus Infections / immunology*
Epstein-Barr Virus Nuclear Antigens / immunology
Female
Herpesvirus 4, Human
Humans
Lymphoproliferative Disorders / virology*
Male
Middle Aged
Organ Transplantation / adverse effects*
Postoperative Complications / immunology
Reverse Transcriptase Polymerase Chain Reaction
Viral Load
Chemical
Reg. No./Substance:
0/EBV-encoded nuclear antigen 1; 0/Epstein-Barr Virus Nuclear Antigens

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