Bocchieri M H, Sabol J L, O'Neill D K
Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pa.
Gerontology. 1988;34(5-6):221-30. doi: 10.1159/000212959.
The leukemia-prone C58 strain of mouse was examined for age-related changes in cellular immune function. Proliferative responses of lymphocytes to autologous and allogeneic stimulator cells [autologous mixed lymphocyte response (AMLR) and mixed lymphocyte response (MLR), respectively] and to mitogens were tested both prior to and around the usual age of disease onset which occurs at 7-8 months. Leukemia in these animals was defined by elevated peripheral blood and splenic white blood cell counts. The AMLR declined greater than 30% by 6-7 months of age and was virtually absent by 8 months of age even in animals that were not overtly leukemic. The MLR declined precipitously (greater than 95%) at 9 months of age. Both declines occurred at a younger age in C58 mice than in nonleukemic strains. Mixing experiments with cells from young and old animals indicate a defect in the Ly 1+23-, L3T4+ responding T cells. No evidence indicating a role for suppressor cell activity in this decline of cell-mediated immunity could be found. Deficiencies in cytokine (IL-2 and IL-1) production were not observed except in the oldest mice tested. Around the usual time of disease onset, splenic natural killer (NK) cell activity declines sharply even in nonleukemic mice. Cell-mixing experiments showed no evidence of suppressor cell activity by spleen cells from older mice, leukemic or nonleukemic, on the NK cell activity of young adult animals. Interferon alpha, beta treatment enhanced the NK activity of cells from old mice but did not restore the level of activity seen in young mice. Evidence has therefore been found for a premature decline in cellular immune function in two responses with proposed immunoregulatory roles, the AMLR and NK cell activity. It is possible that their decline could play a predisposing role in the onset of this retroviral leukemia or that these cell populations may be the target of the retrovirus.
对易患白血病的C58品系小鼠进行了细胞免疫功能与年龄相关变化的研究。在通常发病年龄（7 - 8个月）之前及左右，分别检测淋巴细胞对自体和异体刺激细胞的增殖反应[分别为自体混合淋巴细胞反应（AMLR）和混合淋巴细胞反应（MLR）]以及对有丝分裂原的反应。这些动物的白血病通过外周血和脾脏白细胞计数升高来定义。到6 - 7月龄时，AMLR下降超过30%，到8月龄时几乎消失，即使在没有明显白血病的动物中也是如此。MLR在9月龄时急剧下降（超过95%）。C58小鼠中这两种反应的下降发生年龄比非白血病品系小鼠更小。用年轻和年老动物的细胞进行混合实验表明，Ly 1 + 23 -、L3T4 +反应性T细胞存在缺陷。未发现有证据表明抑制细胞活性在这种细胞介导免疫的下降中起作用。除了所检测的最老的小鼠外，未观察到细胞因子（IL - 2和IL - 1）产生的缺陷。在通常发病时间左右，即使在非白血病小鼠中，脾脏自然杀伤（NK）细胞活性也会急剧下降。细胞混合实验表明，无论是白血病还是非白血病的老年小鼠的脾细胞，对年轻成年动物的NK细胞活性均无抑制细胞活性的证据。α、β干扰素治疗可增强老年小鼠细胞的NK活性，但不能恢复到年轻小鼠的活性水平。因此，已发现两种具有免疫调节作用的反应，即AMLR和NK细胞活性，其细胞免疫功能过早下降。它们的下降可能在这种逆转录病毒白血病的发病中起易感作用，或者这些细胞群体可能是逆转录病毒的靶标。
