Activation and adoptive transfer of Epstein-Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease

Khanna, R., Bell, S., Sherritt, M., Galbraith, A., Burrows, S. R., Rafter, L., Clarke, B., Slaughter, R., Falk, M. C., Douglass, J., Williams, T., Elliott, S. L. and Moss, D. J. (1999) Activation and adoptive transfer of Epstein-Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease. Proceedings of the National Academy of Sciences of the United States of America, 96 18: 10391-10396.


Author Khanna, R.
Bell, S.
Sherritt, M.
Galbraith, A.
Burrows, S. R.
Rafter, L.
Clarke, B.
Slaughter, R.
Falk, M. C.
Douglass, J.
Williams, T.
Elliott, S. L.
Moss, D. J.
Title Activation and adoptive transfer of Epstein-Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
Publication date 1999-08-31
Sub-type Article
DOI 10.1073/pnas.96.18.10391
Volume number 96
Issue number 18
ISSN 0027-8424
1091-6490
Start page 10391
End page 10396
Total pages 6
Place of publication Washington, DC, USA
Publisher National Academy of Sciences
Collection year 1999
Language eng
Subject C1
320206 Tumor Immunology
730108 Cancer and related disorders
Abstract The treatment of Epstein-Barr virus (EBV)associated lymphoproliferative disease (PTLD) in EBV seronegative solid organ transplant recipients who acquire their EBV infection after engraftment poses a considerable challenge because of underlying immunosuppression that inhibits the virus-specific cytotoxic T cell (CTL) response in vivo. We have developed a protocol for activating autologous EBV-specific CTL lines from these patients and show their potential use for immunotherapy against PTLD in solid organ transplant patients. Peripheral blood mononuclear cells from a panel of solid organ transplant recipients with and without active PTLD were used to assess EBV-specific memory CTL responses. The activation protocol involved cocultivation of peripheral blood mononuclear cells with an autologous lymphoblastoid cell line under conditions that favored expansion of virus-specific CTL and hindered the proliferation of allospecific T cells. These CTL consistently showed (i) strong EBV-specificity, including reactivity through defined epitopes in spite of concurrent immunosuppressive therapy, and (ii) no alloreactivity toward donor alloantigens. More importantly, adoptive transfer of these autologous CTLs into a single patient with active PTLD was coincident with a very significant regression of the PTLD, These results demonstrate that a potent EBV-specific memory response can be expanded from solid organ recipients who have acquired their primary EBV infection under high levels of immunosuppressive therapy and that these T cells may have therapeutic potential against PTLD.
Keyword Immunology
Lymphocytes
Recipients
Infection
Lymphoma
Disorders
Immunity
Antigens
Q-Index Code C1

Document type: Journal Article
Sub-type: Article
Collections: School of Population Health Publications
School of Medicine Publications
 
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