Cao Ling, Hudson Chad A, Lawrence David A
Laboratory of Clinical and Environmental Endocrinology and Immunology, Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA.
Toxicol Sci. 2003 Aug;74(2):325-34. doi: 10.1093/toxsci/kfg146. Epub 2003 May 28.
Experiments were conducted to delineate the cellular changes modulated by acute cold/restraint stress (ACRS), a physical and psychological stressor, in response to a Listeria monocytogenes(LM) infection. In addition to wild type (WT) BALB/c mice, CD4-deficient (CD4-/-) BALB/c mice, which have no effective adaptive immunity, were used to determine the involvement of adaptive versus innate immunity. ACRS-induced suppression of host resistance to LM was not observed in CD4-/- mice, suggesting the involvement of CD4+T cells in the acute cold/restraint stress (ACRS)-induced inhibition. The in vivo splenic leukocyte phenotypes and activities of WT BALB/c mice after infection and in vitro lymphocyte responses to heat-killed LM (HKLM) also were examined. There were no significant differences in the numbers of splenic T and B lymphocytes, natural killer cells, macrophages, or neutrophils between nonstressed and ACRS-treated WT mice. However, higher levels of activated T cells and non-T lymphocytes were observed in the ACRS-treated mice; beta-adrenergic receptor (beta-ADR) antagonists (propranolol and atenolol) eliminated these elevated levels of activation, as well as the ACRS-induced suppression of host resistance. ACRS and control mice also had equivalent activation of macrophages. With in vitro HKLM stimulation, splenocytes from ACRS-treated mice produced significantly higher levels of IFNgamma and slightly higher levels of IL-6 in comparison with the nonstressed mice, although equivalent levels of lymphocyte proliferation were obtained. Additionally, ACRS-treated mice showed comparable elevation of serum nitric oxide after infection, indicating macrophage bactericidal activity similar to nonstressed mice. Thus, it appears that ACRS inhibits host resistance through regulatory CD4+ T cells and/or effector cell functions downstream of CD4+ T cell activation, as well as through beta-ADR signaling, in that blockage of these receptors appears to aid host defenses by means other than elevation of helper T cell activity. Because CD4 T cell deficiency and beta-ADR blockage produced equivalent effects, beta-ADR+ CD4+ T cells may have a negative role on host defenses after ACRS.
进行实验以描述由急性冷/束缚应激（ACRS，一种生理和心理应激源）调节的细胞变化，该应激源是对单核细胞增生李斯特菌（LM）感染的反应。除野生型（WT）BALB/c小鼠外，还使用了缺乏有效适应性免疫的CD4缺陷型（CD4-/-）BALB/c小鼠，以确定适应性免疫与先天性免疫的参与情况。在CD4-/-小鼠中未观察到ACRS诱导的宿主对LM抵抗力的抑制，这表明CD4+T细胞参与了急性冷/束缚应激（ACRS）诱导的抑制作用。还检查了感染后WT BALB/c小鼠的体内脾白细胞表型和活性，以及体外淋巴细胞对热灭活LM（HKLM）的反应。在未应激和ACRS处理的WT小鼠之间，脾T淋巴细胞、B淋巴细胞、自然杀伤细胞、巨噬细胞或中性粒细胞的数量没有显著差异。然而，在ACRS处理的小鼠中观察到更高水平的活化T细胞和非T淋巴细胞；β-肾上腺素能受体（β-ADR）拮抗剂（普萘洛尔和阿替洛尔）消除了这些升高的活化水平，以及ACRS诱导的宿主抵抗力抑制。ACRS小鼠和对照小鼠的巨噬细胞也具有同等程度的活化。在体外HKLM刺激下，与未应激小鼠相比，ACRS处理小鼠脾脏细胞产生的IFNγ水平显著更高，IL-6水平略高，尽管获得了同等水平的淋巴细胞增殖。此外，ACRS处理小鼠在感染后血清一氧化氮水平有类似升高，表明巨噬细胞杀菌活性与未应激小鼠相似。因此，似乎ACRS通过调节性CD4+T细胞和/或CD4+T细胞活化下游的效应细胞功能，以及通过β-ADR信号传导来抑制宿主抵抗力，因为阻断这些受体似乎通过除提高辅助性T细胞活性之外的其他方式帮助宿主防御。由于CD4 T细胞缺陷和β-ADR阻断产生了同等效果，β-ADR+CD4+T细胞可能在ACRS后对宿主防御起负面作用。
