Acute Lethal Injury of Lung and Liver in Mice Transplanted With Ex Vivo-Expanded CTLs
Abstract:Clinical application of cytotoxic T lymphocytes (CTL) induced in vitro is extensively used for the treatment of viral infection and malignant diseases. We produced anti H-2d CTL in vitro from C57BL/6 (B6) splenocytes presensitized with (B6 × DBA/2) F1 (BDF1) splenocytes to establish a model system of CTL therapy. The specificity and cytotoxic activity were high enough (E/T ratio 1:1 = 38.8%) to induce graft versus host reaction. Though the total number of B6 splenocytes decreased by 0.27 during the 4 days of culture, the number of CD8+ lymphocytes increased 1.3-fold. When more than 5 × 106 cells of H-2d-reactive CTL were transplanted into BDF1 mice, mice died within 2 days postinduction. This lethal effect was not seen in the mice induced with ConA-stimulated T cells. Histological examination of the lungs and liver revealed massive infiltration of neutrophils in alveoli and the necrosis of hepatocytes. Therefore, this protocol was shown to be effective to produce alloantigen-specific CTLs and applicable to in vitro manipulation such as retrovirus-mediated gene transfer.
Document Type: Research Article
Affiliations: 1: *Research Center for Genetic Engineering and Cell Transplantation, Tokai University School of Medicine, Isehara, Kanagawa, Japan 2: †Department of Hematology, Tokai University School of Medicine, Isehara, Kanagawa, Japan 3: ‡Department of Pediatrics, Tokai University School of Medicine, Isehara, Kanagawa, Japan
Publication date: April 1, 2001
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