Acute lethal injury of lung and liver in mice transplanted with ex vivo-expanded CTLs.
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 x 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 x 10(6) 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.
Sato
T
T
Research Center for Genetic Engineering and Cell Transplantation, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Ando
K
K
Oki
T M
TM
Miyatake
H
H
Matsuzawa
H
H
Hotta
T
T
Kato
S
S
D000818:Animals; D017690:Cell Transplantation; D002478:Cells, Cultured; D002857:Chromium / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology / Q000503:physiopathology*; D008099:Liver / Q000473:pathology*; D008168:Lung / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D011650:Pulmonary Alveoli / Q000473:pathology; D013154:Spleen / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D014185:Transplantation, Isogeneic
D002857:Chromium; D003208:Concanavalin A