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

Item Type:	Article
Title:	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
Creators Name:	Sebelin-Wulf, K. and Nguyen, T.D. and Oertel, S. and Papp-Vary, M. and Trappe, R. and Schulzki, A. and Pezzutto, A. and Riess, H. and Subklewe, M.
Abstract:	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/mul 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/mul+/-161 vs. controls 1008/mul+/-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/mul) were associated with an elevated EBV load (>1000 copies/mug 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.
Keywords:	EBV, PTLD, CD8 T cells, CD4 T cells, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Count, Epstein-Barr Virus Infections, Epstein-Barr Virus Nuclear Antigens, Human Herpesvirus 4, Lymphoproliferative Disorders, Organ Transplantation, Postoperative Complications, Reverse Transcriptase Polymerase Chain Reaction, Viral Load
Source:	Transplant Immunology
ISSN:	0966-3274
Publisher:	Elsevier
Volume:	17
Number:	3
Page Range:	203-210
Date:	April 2007
Official Publication:	https://doi.org/10.1016/j.trim.2006.10.006
PubMed:	View item in PubMed

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