Activation and adoptive transfer of Epstein-Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease.
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.
Khanna
R
R
Epstein-Barr Virus Unit, Queensland Institute of Medical Research and University of Queensland Joint Oncology Program, Brisbane 4006, Australia.
Bell
S
S
Sherritt
M
M
Galbraith
A
A
Burrows
S R
SR
Rafter
L
L
Clarke
B
B
Slaughter
R
R
Falk
M C
MC
Douglass
J
J
Williams
T
T
Elliott
S L
SL
Moss
D J
DJ
D019264:Adoptive Transfer; D000328:Adult; D002460:Cell Line; D002461:Cell Line, Transformed; D005260:Female; D016027:Heart Transplantation / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology; D016040:Lung Transplantation / Q000276:immunology; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation / Q000276:immunology; D011183:Postoperative Complications / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014181:Transplantation Immunology