Dendritic cells improve the generation of Epstein-Barr virus-specific cytotoxic T lymphocytes for the treatment of posttransplantation lymphoma.
BACKGROUND
The use of immunosuppressive therapies after solid organ transplantation has been shown to increase a patient's risk for Epstein-Barr virus (EBV)-associated lymphoma. A potential therapy for this disorder is the adoptive transfer of EBV-specific cytotoxic T lymphocytes (CTLs). We proposed that dendritic cells (DCs) could be loaded with EBV antigens and be used to improve the in vitro generation of EBV-specific CTLs.


METHODS
Autologous EBV-transformed B-lymphoblastoid cell lines (BLCLs) were generated from normal donors, and CTLs were initiated by culturing peripheral blood mononuclear cells with DCs alone, disrupted BLCLs alone, intact, irradiated BLCLs alone, and DCs loaded with disrupted BLCLs. Lytic activities were determined with a 4-hour chromium-release assay against autologous BLCLs, and statistical calculations were performed by a Student t test assuming equal variance.


RESULTS
The lytic activity of CTLs generated with DCs loaded with disrupted BLCLs reached 78% and was statistically significant (P < .01) at all effector/target ratios compared with CTLs generated with DCs alone, disrupted BLCLs alone, or intact BLCLs alone. Total numbers of CTLs were also greater than those of control groups for DCs loaded with disrupted BLCLs.


CONCLUSIONS
DCs improved the in vitro generation of EBV-specific CTLs as evidenced by this group's significantly increased lytic activity over that of the control group. The improved lytic activity of DC-generated EBV-CTLs suggests that adoptive transfer of these cells could lead to a more effective immunotherapeutic response against posttransplantation EBV-associated lymphoma.
Wheatley
G H
GH
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
McKinnon
K P
KP
Iacobucci
M
M
Mahon
S
S
Gelber
C
C
Lyerly
H K
HK
D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002860:Chromium Radioisotopes; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008213:Lymphocyte Activation / Q000276:immunology; D008223:Lymphoma / Q000209:etiology / Q000276:immunology / Q000821:virology*; D016377:Organ Transplantation; D011183:Postoperative Complications / Q000276:immunology / Q000821:virology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology*
D000956:Antigens, Viral; D002860:Chromium Radioisotopes; D007166:Immunosuppressive Agents