Interferon-γ (IFN-γ) plays a vital role to protect mice from tumor development. Spontaneous lymphoma was observed at high incidence in in Ifngr1 mutant mice on a NOD genetic background, and 71 of 73 lymphomas were T cell lymphomas. However, DP and SP lymphomas did not express intracellular and surface TCRb , which means lymphomas originate from immature DN T cells before TCRb rearrangement.
Even IFN-g signalling is important for immune surveillance. However, it is still a doubt whether IFN-g deficiency affected T cell development in early stage and increased T cell lymphomagenesis risk.
Due to the lymphoma original from thymocytes before TCRb selection, we focus on investigating the IFN-g deficiency effect on the TCR rearrangement. Recombination activating genes (Rag1 and Rag2) was measured in DN1-DN4 and DP thymocytes and found no difference between NOD and Ifngr1 mutant mice. Therefore, Ifngr1 mutant mice can normally express Rags for introducing double strand breaks (DSB) and DNA binding activities. P53 pathway is important tomaintain genomic stability by sensing DNA damage and repairing the DSB. P53 phosphorylation level was tested in NOD and Ifngr1 mutant thymocytes after γ radiation and the p-P53 expression in NOD is same as that in Ifngr1 mutant thymocytes. As a result, different stage thymocyte percentage is compared and found similar between NOD and Ifngr1mutant mice, which means IFN-g deficiency did not impair the T cell development and thymocytes phenotype.
In our study, we characterize the spontaneous lymphoma in Ifngr1 mutant mice is immature T cell origin and confirmed the IFN-g deficiency did not affect TCR rearrangement and thymocytes development. Combined with IFN-gR deficiency in the host enables the transfer of secondary lymphomas, we conclude that IFN-g signaling deficiency does not increase T cell lymphomagenesis risk, but IFN-g non-sensitive immune system failure to supress T cell lymphoma development.