Severe immune dysfunction after lethal neutron irradiation in a JCO nuclear facility accident victim.

The optimal treatment for the hematological toxicity of acute radiation syndrome (ARS) is not fully established, especially in cases of high-dose nonuniform irradiation by mixed neutrons and gamma-rays, because estimation of the irradiation dose (dosimetry) and prediction of autologous hematological recovery are complicated. For the treatment of ARS, we performed HLA-DRB1-mismatched unrelated umbilical cord blood transplantation (CBT) for a nuclear accident victim who received 8 to 10 GyEq mixed neutron and gamma-ray irradiation at the JCO Co. Ltd. nuclear processing facility in Tokaimura, Japan. Donor/ recipient mixed chimerism was attained; thereafter rapid autologous hematopoietic recovery was achieved in concordance with the termination of immunosuppressants. Immune function examined in vitro showed recovery of the autologous immune system was severely impaired. Although the naive T-cell fraction and the helper T-cell subtype 1 fraction were increased, the mitogenic responses of T-cells and the allogeneic mixed leukocyte reaction were severely suppressed. Endogenous immunoglobulin production was also suppressed until 120 days after the accident. Although skin transplantation for ARS was successful, the patient died of infectious complications and subsequent acute respiratory distress syndrome 210 days after the accident. These results suggest that fast neutrons in doses higher than 8 to 10 Gy cause complete abrogation of the human immune system, which may lead to fatal outcome even if autologous hematopoiesis recovers. The roles of transplantation, autologous hematopoietic recovery, chimerism, immune suppression, and immune function are discussed.

Effect of Tumor Vaccine of EL-4 Cell Transduced with IL-12 Gene in C57BL/6 Mice / 中国实验血液学杂志

In order to study the vaccine potency of gene-modified tumor cells, IL-12 express vector was constructed by using retrovirus. The vector was transfected into EL-4 thymic lymphoma cells and the effect of transfectant on anti-tumor immunity was investigated. The tumorigenicity of EL-4/IL-12 transfectant in syngeneic C57BL/6 mice was decreased significantly after implanted with EL-4/IL-12 transfectant compared with EL-4/Wt or EL-4/Neo groups (P < 0.001). The systemic protective immunity was induced against the challenge with EL-4/Wt (in 8/10 mice) after the rejection of EL-4/IL-12 in vivo experiment, a stronger CTL activity against EL-4/Wt cells and a weak killer activity against syngeneic Lewis lung carcinoma (LLC) cells were obtained in (51)Cr release assay. In vivo depletion analysis suggested that the decreased tumorigenicity mainly depended on CD4(+), CD8(+) and NK cells. Therapeutic vaccines with EL-4/IL-12 cells could retard the growth of established EL-4/Wt tumors significantly compared with those of EL-4/Neo (P < 0.005). These studies suggested that immunotherapy and gene therapy using IL-12 is effective in hematopoietic malignancy and IL-12 has prospects of application in human cancer treatment in the near future.