Reconstitution of the latent T-lymphocyte response to Epstein-Barr virus is coincident with long-term recovery from post-transplant lymphoma after adoptive immunotherapy

Sherritt, M. A., Bharadwaj, M., Burrows, J. M., Morrison, L. E., Elliott, S. L., Davis, J. E., Kear, L. M., Slaughter, R. E., Bell, S. C., Galbraith, A. J., Khanna, R. and Moss, D. J. (2003) Reconstitution of the latent T-lymphocyte response to Epstein-Barr virus is coincident with long-term recovery from post-transplant lymphoma after adoptive immunotherapy. Transplantation, 75 9: 1556-1560. doi:10.1097/01.TP.0000058745.02123.6F


Author Sherritt, M. A.
Bharadwaj, M.
Burrows, J. M.
Morrison, L. E.
Elliott, S. L.
Davis, J. E.
Kear, L. M.
Slaughter, R. E.
Bell, S. C.
Galbraith, A. J.
Khanna, R.
Moss, D. J.
Title Reconstitution of the latent T-lymphocyte response to Epstein-Barr virus is coincident with long-term recovery from post-transplant lymphoma after adoptive immunotherapy
Journal name Transplantation   Check publisher's open access policy
ISSN 0041-1337
Publication date 2003-05-01
Sub-type Article (original research)
DOI 10.1097/01.TP.0000058745.02123.6F
Volume 75
Issue 9
Start page 1556
End page 1560
Total pages 5
Place of publication Baltimore, U.S.A.
Publisher Williams & Wilkins
Collection year 2003
Language eng
Subject C1
320206 Tumor Immunology
730101 Infectious diseases
1103 Clinical Sciences
Formatted abstract
Background. Adoptive transfer of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) has been used to treat EBV-induced posttransplant lymphoproliferative disease (PTLD) in solid-organ recipients. This study defines, in detail, the temporal relationship between adoptive transfer and the clinical response, EBV DNA load, and CTL response to EBV latent and lytic antigens in a patient with a subcutaneous PTLD presentation treated with adoptive transfer of autologous CTL.
Methods.
A heart transplant patient developed multiple subcutaneous PTLD deposits and was treated with a total of six doses (20 X 10(6) CTL per dose) of cultured autologous polyclonal EBV-specific CTL by adoptive transfer.
Results.
Complete regression occurred after the sixth CTL dose, and the patient has remained disease-free from 47 weeks to the present (136 weeks). Realtime polymerase chain reaction analysis showed a reduction in viral load after therapy. Enzyme-linked immunospot analysis using defined EBV CTL epitopes showed that the CTL precursor frequency (pCTL) toward a lytic antigen epitope was elevated early in the course of disease but tended to decrease to lower levels after long-term regression of PTLD. The most dramatic result was seen in relation to three latent CTL epitopes studied. Long-term regression of PTLD was characterized by high pCTL toward the latent antigens.
Conclusions. Increased pCTL reactivity to latent EBV CTL epitopes is coincident with recovery from disease after adoptive transfer of autologous CTL. Furthermore, the results are compatible with the belief that activation of a sustained CTL response to EBV latent epitopes is protective and may be a characteristic of patients in long-term remission from PTLD.
Keyword Immunology
Surgery
Transplantation
Organ Transplant Recipients
Lymphoproliferative Disease
Cell Responses
Ebv
Infection
Disorders
Load
Individuals
Immunity
Assay
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2004 Higher Education Research Data Collection
School of Medicine Publications
 
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