A type of rat hepatosplenic gamma-delta (gammadalta) T-cell lymphoma developed after injections with hepatocyte growth factor (HGF) oligonucleotides, which was rejected by surviving syngeneic spleen graft.
The transduction of exogenous hepatocyte growth factor (HGF) genes to spleen T lymphocytes and the immune effects of syngeneic spleen graft on spleen lymphoma cells were studied in LEW/Sea rats. Three different systems were designed. (1) Six female rats and six male rats received irradiated spleen graft and were followed for 7 months. (2) Five female rats and six male rats received intra-peritoneal (i.p.) injections of the Lewis red cells incorporated 20-bp HGF genes and anti-interleukin-6 (IL-6) antibody (Ab) with spleen graft and were followed for 5.5 months. (3) Four females and five males received i.p. injections of the Lewis red cells incorporated 20-bp HGF genes and anti-IL-6 Ab without spleen graft and were followed for 5.5 months. Hemato-pathological analyses, flow cytometer analyses of gamma-delta (gammadelta) T-cell receptor (TCR)-positive lymphocytes and reverse-transcription-polymerase chain reaction (RT-PCR) of TCRgamma gene, TCRValpha3 gene and apoptotic genes were performed. Results showed that one of the six females received irradiated spleen graft developed nodal gamma-delta (gammadelta) T-cell pre-lymphoma with 100% of gammadelta TCR+ lymphocytes in the mesenteric lymph nodes. One female injected with the HGF genes and anti-IL-6 Ab and grafted spleen died of advanced hepatosplenic gammadelta T-cell lymphoma at 3.5 month observation. All the five males injected with the HGF genes and anti-IL-6 Ab without spleen graft developed early hepatosplenic gammadelta T-cell lymphoma at 5.5 month observation. In two rats with spleen graft and the two rats without spleen graft, which were injected with the HGF genes and anti-IL-6 Ab, the lymphoma was suspected uncertainly with activated TCRValpha3 mRNA. The i.p. injections of HGF genes, which were incorporated in the red blood cells, triggered hapatosplenic gammadelta T-cell lymphoma. Surviving spleen graft rejected the lymphoma cells, but not in rats rejected the graft. Spleen graft was a good organ transplantation to expect graft versus lymphoma effects.
Nakatsuji
Tadako
T
Department of Transfusion, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. nh80415@hama-med.ac.jp
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D019672:Genes, T-Cell Receptor / Q000235:genetics; D020350:Graft vs Tumor Effect; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D015850:Interleukin-6 / Q000276:immunology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000209:etiology / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology; D008297:Male; D009841:Oligonucleotides / Q000008:administration & dosage / Q000009:adverse effects*; D016377:Organ Transplantation; D016133:Polymerase Chain Reaction; D051381:Rats; D011917:Rats, Inbred Lew; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000235:genetics*; D013154:Spleen / Q000276:immunology / Q000637:transplantation*; D013160:Splenic Neoplasms / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology; D014185:Transplantation, Isogeneic
D000906:Antibodies; D015850:Interleukin-6; D009841:Oligonucleotides; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017228:Hepatocyte Growth Factor