|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1997 : ¥300,000 (Direct Cost : ¥300,000)
Fiscal Year 1996 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1995 : ¥1,200,000 (Direct Cost : ¥1,200,000)
It has been demonstrated that macrophages play an important role for the maintenance of homeostasis of several tissues by secreting a variety of cytokines. Recent studies have revealed that cytokine networks are involved in the development and evolution of thymic lymphpomas, In order to clarify the cytokines associated with the development of thymic lymphomas induced by X-rays in B6C3F1 mice, we first characterized the T-cell subsets after irradiation by quantifying the mRNA of cytokine receptors (IL-1R, IL-2, IL-4R, IL-6R, IL-7R, IL-9R, IL-15R, TNFR type-1, TNFR type-2, c-kit, Flt-3) with RT-PCR.The results indicated the immediate appearance of immature T-cell subsets positive for IL-1R, IL-2R and IL-7R, This was coincident with the increased expression of IL-1 and IL-7 by thymic stromal cells (macrophages), suggesting a paracrine loop of IL-1 and IL-7 for the survival and proliferation of immature thymocytes after irradiation. We also found thatT-cell subset positive for IL-9R appeared 12 weeks after irradiation when the first lymphoma was identified. Since IL-9 receptor was expressed in -9O% of thymic lymphomas and was a major anti-apoptotic factor for thymic lymphomas, this late appearing subset with IL-9R could be considered to contain pre-lymphoma cells. Thus, IL-9/IL-9R loop seems to contribute to the development of thymic lymphomas at promotion / progression stages. However, this IL-9R expressing T-cell subset failed to increase in aging mice after irradiation, suggesting a lack of the induction of 1L9 / IL9R loop could be ascribed to the resistance to radiogenic lymphomagenesis in aging mice.