James S J, Enger S M, Peterson W J, Makinodan T
Geriatric Research, Education and Clinical Center, VA Medical Center, West Los Angeles, California 90073.
Clin Immunol Immunopathol. 1990 Jun;55(3):427-37. doi: 10.1016/0090-1229(90)90129-e.
Very low doses of ionizing radiation can enhance immune responsiveness and extend life span in normal mice. Total lymphoid irradiation at relatively high doses of radiation can retard autoimmune disease in genetically susceptible mice, but may impair immune function. In order to determine whether fractionated low dose exposure would enhance immune response and retard lymphadenopathy in autoimmune-prone mice, groups of C57B1/6 lpr/lpr mice were sham irradiated, exposed 5 days/week for 4 weeks to 0.04 Gy/day (0.8 Gy cumulative dose), or to 0.1 Gy/day (2.0 Gy cumulative dose). After the radiation protocol, the mice were evaluated for splenic T cell proliferative capacity, T cell subset distribution, and total spleen cell numbers. The independent and additive effect of caloric restriction was additionally assessed since this intervention has been shown to increase immune responsiveness and retard disease progression in autoimmune-prone mice. The congenic C57B1/6 +/+ immunologically normal strain was evaluated in parallel as congenic control. The results indicated that mitogen-stimulated proliferation was up-regulated in both strains of mice after exposure to 0.04 Gy/day. The proliferative capacity was additively enhanced when radiation at this dose level was combined with caloric restriction. Exposure to 0.1 Gy/day resulted in further augmentation of proliferative response in the lpr/lpr mice, but was depressive in the +/+ mice. Although the proportions of the various T cell subpopulations were altered in both strains after exposure to LDR, the specific subset alterations were different within each strain. Additional experiments were subsequently performed to assess whether the thymus is required for LDR-induced immune potentiation. Thymectomy completely abrogated the LDR effect in the +/+ mice, suggesting that thymic processing and/or trafficking is adaptively altered with LDR in this strain. In contrast, augmentation in proliferative activity after LDR in the lpr/lpr mice was maintained, although attenuated, in thymectomized mice. Taken together, these results indicate that fractionated exposure to LDR augments the proliferative response of spleen cells in both autoimmune-prone and immunologically normal mice; however, within each strain, the mechanisms appear to be different.
极低剂量的电离辐射可增强正常小鼠的免疫反应性并延长其寿命。相对高剂量的全身淋巴照射可延缓基因易感小鼠的自身免疫性疾病，但可能损害免疫功能。为了确定分次低剂量照射是否会增强自身免疫易感性小鼠的免疫反应并延缓淋巴结病，将C57B1/6 lpr/lpr小鼠分组，分别进行假照射、每周5天、连续4周每天照射0.04 Gy（累积剂量0.8 Gy）或每天照射0.1 Gy（累积剂量2.0 Gy）。照射方案结束后，评估小鼠的脾T细胞增殖能力、T细胞亚群分布和脾细胞总数。由于已证明这种干预可增加自身免疫易感性小鼠的免疫反应性并延缓疾病进展，因此还评估了热量限制的独立和累加效应。同时评估同基因C57B1/6 +/+免疫正常品系作为同基因对照。结果表明，每天照射0.04 Gy后，两种品系小鼠的丝裂原刺激增殖均上调。当该剂量水平的辐射与热量限制相结合时，增殖能力得到累加增强。每天照射0.1 Gy导致lpr/lpr小鼠的增殖反应进一步增强，但对+/+小鼠有抑制作用。尽管低剂量辐射（LDR）照射后两种品系小鼠的各种T细胞亚群比例均发生改变，但每个品系内的特定亚群改变不同。随后进行了额外的实验，以评估胸腺是否是LDR诱导免疫增强所必需的。胸腺切除术完全消除了+/+小鼠中的LDR效应，表明该品系中胸腺加工和/或运输随LDR发生适应性改变。相反，lpr/lpr小鼠经LDR照射后增殖活性的增强在胸腺切除小鼠中仍得以维持，尽管有所减弱。综上所述，这些结果表明，分次低剂量辐射可增强自身免疫易感性和免疫正常小鼠脾细胞的增殖反应；然而，在每个品系内，机制似乎不同。
