Introduction of OX40 ligand into lymphoma cells elicits anti-lymphoma immunity in vivo.
OBJECTIVE
OX40, a member of the TNF receptor superfamily, and its ligand (OX40L) play crucial roles in induction and maintenance of integrated T cell immune response. Engagement of OX40L delivers a costimulatory signal to T cells. In this study, we investigated whether inoculation of OX40L-transfected EL4, a murine T cell lymphoma cell line, could induce anti-lymphoma immunity in mice.


METHODS
Female C57BL/6 mice were inoculated with 1 x 10(5) cells of parental EL4, OX40L-transfected EL4 (EL4-OX40L), or mock control vector-transfected EL4 (EL4-mock), and then the tumor size, overall survival, CTL activity of spleen cells, and the immunohistochemistry were compared.


RESULTS
While both parental EL4 and EL4-mock grew rapidly, EL4-OX40L was rejected or grew slower than parental EL4 or EL4-mock. Pretreatment of mice with either anti-CD4 or anti-CD8 mAb accelerated the growth of EL4-OX40L, suggesting that both CD4+ and CD8+ T cells were involved in anti-lymphoma immunity. The immunohistochemical study revealed the infiltration of CD8+ T cells into the tumor of EL4-OX40L. In vitro CTL assay demonstrated that spleen cells of mice that had rejected EL4-OX40L had significant cytotoxic activity against parental EL4.


CONCLUSIONS
The gene transfer of OX40L into lymphoma cells is an eligible and efficient modality to induce anti-lymphoma immunity.
Kaneko
Hitomi
H
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Hori
Toshiyuki
T
Yanagita
Soshi
S
Kadowaki
Norimitsu
N
Uchiyama
Takashi
T
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D018014:Gene Transfer Techniques; D007110:Immunity, Active; D016399:Lymphoma, T-Cell / Q000276:immunology* / Q000628:therapy; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D053278:OX40 Ligand; D010446:Peptide Fragments / Q000276:immunology; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D048069:Tumor Necrosis Factors
D000906:Antibodies; D015704:CD4 Antigens; D016827:CD8 Antigens; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D010446:Peptide Fragments; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505717:Tnfrsf4 protein, mouse; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors; C056725:CD4 (76-94)