A Type of Rat Hepatosplenic Gamma-delta (γδ) T-cell Lymphoma Developed after Injections with Hepatocyte Growth Factor (HGF) Oligonucleotides, which was Rejected by Surviving Syngeneic Spleen Graft

Abstract

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 (ip) 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 ip 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 (γ δ ) T-cell receptor (TCR)-positive lymphocytes and reverse-transcription-polymerase chain reaction (RT-PCR) of TCR γ gene, TCRV α 3 gene and apoptotic genes were performed. Results showed that one of the six females received irradiated spleen graft developed nodal gamma-delta (γ δ ) T-cell pre-lymphoma with 100% of γ δ 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 γ δ 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 γ δ 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 TCRV α 3 mRNA. The ip injections of HGF genes, which were incorporated in the red blood cells, triggered hapatosplenic γ δ 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.