Madden K S, Stevens S Y, Felten D L, Bellinger D L
Department of Neurobiology and Anatomy and the Center for Psychoneuroimmunology, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
J Neuroimmunol. 2000 Mar 1;103(2):131-45. doi: 10.1016/s0165-5728(99)00243-x.
In aged Fischer 344 (F344) rats, sympathetic noradrenergic (NA) innervation of the spleen is markedly diminished compared with young rats. To determine if diminished NA innervation can still provide functional signals to splenic T cells, young (3 months old) and old (17 months old) F344 rats were treated with the NA-selective neurotoxin, 6-hydroxydopamine (6-OHDA) to destroy peripheral NA nerve fibers. In 3-month-old rats, no alterations in spleen cell Con A-induced T cell proliferation, IL-2 or IFN-gamma production were observed up to 15 days after sympathectomy, when splenic NE was maximally depleted. By 21 days post-sympathectomy, when NE levels had partially recovered, Con A-induced proliferation and IFN-gamma production, but not IL-2 production, were reduced in sympathectomized animals. After day 21 post-sympathectomy, no alterations in T cell functions were observed in sympathectomized animals. In 17-month-old rats, spleen cell Con A-induced proliferation and IL-2 production were reduced 5 days after sympathectomy in the absence of changes in CD5+ T cells or IFN-gamma production. Desipramine pretreatment, to block 6-OHDA uptake and prevent sympathectomy, completely blocked the 6-OHDA-induced effects, demonstrating that the destruction of NA nerve fibers is required. After day 5 post-sympathectomy, no sympathectomy-induced alterations in Con A-induced T cell functions were observed in old animals. These differences between young and old rats demonstrate that old animals are more susceptible to loss of sympathetic NA innervation, perhaps because compensatory mechanisms are limited. The sympathectomy-induced reduction in T cell proliferation indicates that splenic NA innervation in old animals, though diminished, can exert a positive regulatory influence on T lymphocyte function. Further study of sympathetic neural-immune interactions in the aged rat may provide a means to improve T cell responsiveness in aging.
与年轻大鼠相比，老年费希尔344（F344）大鼠脾脏的交感去甲肾上腺素能（NA）神经支配明显减少。为了确定NA神经支配减少是否仍能向脾T细胞提供功能性信号，对年轻（3个月大）和老年（17个月大）的F344大鼠用NA选择性神经毒素6-羟基多巴胺（6-OHDA）处理，以破坏外周NA神经纤维。在3个月大的大鼠中，直到交感神经切除术后15天，当脾脏去甲肾上腺素（NE）被最大程度耗尽时，未观察到脾细胞刀豆蛋白A（Con A）诱导的T细胞增殖、白细胞介素-2（IL-2）或干扰素-γ（IFN-γ）产生的改变。交感神经切除术后21天，当NE水平部分恢复时，交感神经切除的动物中Con A诱导的增殖和IFN-γ产生减少，但IL-2产生未减少。交感神经切除术后21天之后，在交感神经切除的动物中未观察到T细胞功能的改变。在17个月大的大鼠中，交感神经切除术后5天，脾细胞Con A诱导的增殖和IL-2产生减少，而CD5+T细胞或IFN-γ产生没有变化。用去甲丙咪嗪预处理以阻断6-OHDA摄取并防止交感神经切除术，完全阻断了6-OHDA诱导的效应，表明需要破坏NA神经纤维。交感神经切除术后5天之后，在老年动物中未观察到交感神经切除术诱导的Con A诱导的T细胞功能改变。年轻和老年大鼠之间的这些差异表明，老年动物更容易受到交感NA神经支配丧失的影响，这可能是因为补偿机制有限。交感神经切除术诱导的T细胞增殖减少表明，老年动物脾脏的NA神经支配虽然减少，但仍可对T淋巴细胞功能发挥正向调节作用。对老年大鼠交感神经-免疫相互作用的进一步研究可能为改善衰老过程中T细胞反应性提供一种方法。
