交感神经对受辐照小鼠免疫系统的调节作用
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摘要
放射神经生物学是辐射生物学的一个新的分支,越来越受到国内外辐射生物学研究者的关注。神经、内分泌、免疫诸系统之间存在着相互作用。中枢神经系统与免疫系统之间存在两条途径,其一是下丘脑-垂体-肾上腺轴,另一条是通过自主神经对免疫系统进行调节。目前国内放射神经生物学主要涉及中枢神经在受到电离辐射刺激后的形态学和功能学的改变。国外主要集中在电离辐射作用后生物体的功能学改变。
免疫细胞是辐射最敏感的细胞群体,细胞表面表达多种受体,其中与神经递质结合的受体则是神经系统调控免疫系统的物质基础。神经系统对受辐射机体免疫系统的影响在放射损伤和放射治疗中具有重要的理论和临床价值,但迄今为止有关这方面的研究报道还很缺乏。本试验用6-OHDA阻断外周交感神经传导,通过检测小鼠外周血中淋巴细胞及其亚群细胞数量、IL-2、NO酶和NO合酶的含量、胸腺指数、脾指数等指标的变化来研究交感神经阻断对受辐照小鼠免疫系统的影响,探讨交感神经阻断对受辐照小鼠免疫系统的作用。
结果显示(1)随着辐照剂量的增加,辐照组小鼠淋巴细胞及其各亚群受损加剧;阻断组小鼠淋巴细胞及其各亚群的变化趋势同辐照组,中、高剂量组下降更加明显。(2)辐照组小鼠体重、脾指数、NOS活力、NO含量等在0.2Gy处有最大值,以后随剂量加大,从0.5Gy到3Gy,数值逐渐减少;而胸腺指数随剂量增加而递减。(3)3Gy组小鼠IL-2的含量为3Gy阻断神经组>空白组>3Gy非阻断神经组。
实验表明去甲肾上腺素对受辐照小鼠的免疫系统的恢复有积极的作用。由于交感神经阻断进一步增强了受辐照机体的免疫抑制作用,在放射治疗过程中应避免损伤交感神经。
Radioneurobiology is a new subject of radiobiology. More and more people in and abroad are paying attention to radiobiology. There are interactions among nerve, endocrine system and immune system. There are two ways between central nervous system and immune system, one is hypothalamic-pituitary-adrenal axis, the other one is through autonomic system. This subject involves the morphological and functional changes of central nerve receiving irradiation. There are much more studies in this area abroad, mainly focusing on the functional changes in biotics after irradiation. Immune cell is the most sensible cell group. There are many receptors expressed on the immune cell. The receptor bonded with neural transmitter is the basic of nervous system regulating the immune system. So the study of the nervos system and its influence in immune system has theoretical and clinical value in irradiation curation. But the study in this area is very rare. We used 6-OHDA to block the peripheral transduction of sympathectical nerve. Then we watched the effect of sympathectomy on the immune system by test the changes in quantity of immune cells and its subgroups, IL-2, NO and NOS in the peripheral blood, thymus index and spleen index of irradiated mice.
The results show (1) the more the dosimetry of irradiation is, the more damage causes in immune cells and its groups; the irradiate effect of sympathectomized group is the same as that of the unsympathectomized group, and the mice that received irradiation of mediate and high dose of had much smaller number of immune cells. (2) weight, thymus index, spleen index, NOS, NO have the highest quatity after receiving 0.2Gy irradiation, and declined with the increasing dose. (3) the quantity of IL -2 in the peripheral blood is: 3Gy+S>control>3Gy(S means sympathectomy).
The conclusion shows that NE has positive function for the recovery of mice. The sympathetic nerve should be watched when the patient are receiving irradiation therapy.
免疫细胞是辐射最敏感的细胞群体,细胞表面表达多种受体,其中与神经递质结合的受体则是神经系统调控免疫系统的物质基础。神经系统对受辐射机体免疫系统的影响在放射损伤和放射治疗中具有重要的理论和临床价值,但迄今为止有关这方面的研究报道还很缺乏。本试验用6-OHDA阻断外周交感神经传导,通过检测小鼠外周血中淋巴细胞及其亚群细胞数量、IL-2、NO酶和NO合酶的含量、胸腺指数、脾指数等指标的变化来研究交感神经阻断对受辐照小鼠免疫系统的影响,探讨交感神经阻断对受辐照小鼠免疫系统的作用。
结果显示(1)随着辐照剂量的增加,辐照组小鼠淋巴细胞及其各亚群受损加剧;阻断组小鼠淋巴细胞及其各亚群的变化趋势同辐照组,中、高剂量组下降更加明显。(2)辐照组小鼠体重、脾指数、NOS活力、NO含量等在0.2Gy处有最大值,以后随剂量加大,从0.5Gy到3Gy,数值逐渐减少;而胸腺指数随剂量增加而递减。(3)3Gy组小鼠IL-2的含量为3Gy阻断神经组>空白组>3Gy非阻断神经组。
实验表明去甲肾上腺素对受辐照小鼠的免疫系统的恢复有积极的作用。由于交感神经阻断进一步增强了受辐照机体的免疫抑制作用,在放射治疗过程中应避免损伤交感神经。
Radioneurobiology is a new subject of radiobiology. More and more people in and abroad are paying attention to radiobiology. There are interactions among nerve, endocrine system and immune system. There are two ways between central nervous system and immune system, one is hypothalamic-pituitary-adrenal axis, the other one is through autonomic system. This subject involves the morphological and functional changes of central nerve receiving irradiation. There are much more studies in this area abroad, mainly focusing on the functional changes in biotics after irradiation. Immune cell is the most sensible cell group. There are many receptors expressed on the immune cell. The receptor bonded with neural transmitter is the basic of nervous system regulating the immune system. So the study of the nervos system and its influence in immune system has theoretical and clinical value in irradiation curation. But the study in this area is very rare. We used 6-OHDA to block the peripheral transduction of sympathectical nerve. Then we watched the effect of sympathectomy on the immune system by test the changes in quantity of immune cells and its subgroups, IL-2, NO and NOS in the peripheral blood, thymus index and spleen index of irradiated mice.
The results show (1) the more the dosimetry of irradiation is, the more damage causes in immune cells and its groups; the irradiate effect of sympathectomized group is the same as that of the unsympathectomized group, and the mice that received irradiation of mediate and high dose of had much smaller number of immune cells. (2) weight, thymus index, spleen index, NOS, NO have the highest quatity after receiving 0.2Gy irradiation, and declined with the increasing dose. (3) the quantity of IL -2 in the peripheral blood is: 3Gy+S>control>3Gy(S means sympathectomy).
The conclusion shows that NE has positive function for the recovery of mice. The sympathetic nerve should be watched when the patient are receiving irradiation therapy.
引文
[1] Lawrence Steinman. Elaborate interactions between the immune and nervous systems[J]. Nature Immunology, 2004, 5(3): 575~581.
[2] Adam P, Kohm, Virginia M. Sanders. Norepinephrine: a messenger from the brain to the immune system[J]. Immunology Today, 2000, 21(11): 539~542.
[3] Sternberg E M. Neural-immune interactions in health and disease[J]. Annals of New York Academy of Sciences, 1997, 100(11): 20~27.
[4] Straub R H. Complexity of the bi-directional neuroimmune junction in the spleen[J]. Trends in Pharmacological Sciences, 2004, 25(12): 640~646.
[5] Brogden K A, Guthmiller J M, Salzet M, et al. The nervous system and innate immunity: the neuropeptide connection[J]. Nature Immunology, 2005, 6(6): 558~564.
[6] Webster J I, Tonelli L, Sternberg EM. Neuroendocrine regulation of immunity[J]. Annual Review of Immunology, 2002, 20:125~163.
[7] Delgado M, Pozo D, Ganea D. The significance of vasoactive intestinal peptide in immunomodulation[J]. Pharmacologcial Reviews, 2004, 56(2):249~290.
[8] Bulloch K, Moore R Y. Innervation of the thymus gland by brain stem and spinal cord in mouse and rat[J]. American Journal of Anatomy, 1981, 162(2): 157~166.
[9] Bulloch K, Pomerantz W. Autonomic nervous system innervation of thymic related lymphoid tissue in wild-type and nude mice[J]. Journal of Comparative Neurology, 1984, 228(1): 57~68.
[10] Nance D M, Hopkins D A, Bieger D. Re-investigation of the innervation of the thymus gland in mice and rats[J]. Brain, Behavior and Immunology, 1987, 1(2): 134~147.
[11] Nicholas Trotter, Ruth L Stornetta. Transneuronal mapping of the CNS network controlling sympathetic outflow to the rat thymus[J]. Autonomic Neuroscience: Basic and Clinical, 2007, 131(1-2): 9~20.
[12] Wan W, Wetmore L, Sorensen C M, et al. Neural and biochemical mediators of endotoxin and stress-induced c-fos expression in the rat brain[J]. Brain Research Bulletin., 1994. 34(1): 7~14.
[13] Nance D M, Burns J. Innervation of the spleen in the rat: evidence for absence of afferent innervation[J]. Brain, Behavior and Immunology, 1989, 3(4): 281~290.
[14] Bellinger D L, Lorton D, Hamill R W, et al. Acetylcholinesterase staining and choline acetyltransferase activity in the young adult rat spleen: lack of evidence for cholinergicinnervation[J]. Brain, Behavior and Immunology, 1993, 7(3): 191~204.
[15] Schafer M K., Eiden L E, Weihe E. Cholinergic neurons and terminal fields revealed by immunohistochemistry for the vesicular acetylcholine transporter. II. The peripheral nervous system[J]. Neuroscience, 1998, 84(2): 361~376.
[16] Cano G, Sved A F, Rinaman L, et al. Characterization of the central nervous system innervation of the rat spleen using viral transneuronal tracing[J]. Journal of Comparative Neurology, 2001, 439(1): 1~18.
[17] Nicholas W K, Virginia M S. It takes nerve to tell T and B cells what to do[J]. Journal of Leukocyte Biology, 2006, 79: 1093~1104.
[18] Sanders V M, Kasprowicz D J, Kohm A P, et al. Neurotransmitter receptors on lymphocytes and other lymphoid cells, third ed[M]. In: Ader, R., Felten, D., Cohen, N. (Eds.) Psychoneuro -immunology, 2001, 2: 161~196.
[19] Kavelaars A. Regulated expression of alpha-1 adrenergic receptors in the immune system[J]. Brain Behav. Immun., 2002, 16(6): 799~807.
[20] Ignatowski T A, Gallant S., Spengler R.N. Temporal regulation by adrenergic receptor stimulation of macrophage (M phi)-derived tumor necrosis factor (TNF) production post LPS challenge[J]. Journal of Neuroimmunology, 1996, 65(2): 107~117.
[21] Meltzer J C, MacNeil B J, Sanders V., et al. Stress-induced suppression of in vivo splenic cytokine production in the rat by neural and hormonal mechanisms[J]. Brain, Behavior and Immunology, 2004, 18(3): 262~273.
[22] Sanders V M, Munson A E. Norepinephrine and the antibody response[J]. Pharmacologcial Reviews, 1985, 37(3): 229~248.
[23] Sanders V M, Kasprowicz D J, Swanson-Mungerson M A, et al. Adaptive immunity in mice lacking the beta2-adrenergic receptor[J]. Brain, Behavior and Immunology, 2003, 17(1): 55~67.
[24] Kohm A P, Sanders V M. Norepinephrine and beta2-adrenergic receptor stimulation regulate CD4+T and B lymphocyte function in vitro and in vivo[J]. Pharmacological Reviews, 2001b, 53(4):487~525.
[25] Madden K S, Felten S Y, Felten D L, et al. Sympathetic neural modulation of the immune system. I. Depression of T cell immunity in vivo and in vitro following chemical sympathectomy[J]. Brain, Behavior and Immunology, 1989, 3(1): 72~89.
[26] Callahan T A, Moynihan J A. The effects of chemical sympathectomy on T-cell cytokine responses are not mediated by altered peritoneal exudate cell function or an inflammatoryresponse[J]. Brain, Behavior and Immunology, 2002, 16(1): 33~45.
[27] Alaniz R C, Thomas S A, Perez-Melgosa M., et al. Dopamine beta-hydroxylase deficiency impairs cellular immunity[J]. The Proceedings of National Academy of Science Usa, 1999, 96(5): 2274~2278.
[28] Kohm A P, Sanders V M. Norepinehrine and beta-2-adrenergic receptor stimulation regulate CD4+T and B lymphocyte function in vitro and in vivo[J]. Pharmacological Reviews, 2001a, 53(3): 487~525.
[29] Sanders V M, Straub R H. Norepinephrine, the beta-adrenergic receptor, and immunity[J]. Brain, Behavior and Immunology, 2002, 16(4): 290~332.
[30] Pongratz G., McAlees J W, Conrad D H, et al. The level of IgE produced by a B Cell is regulated by norepinephrine in a p38 MAPK- and CD23-dependent manner[J]. Journal of Immunology, 2006, 177(5): 2926~2938.
[31] Simon C, Csiky B. Effect of neonatal sympathectomy on the development of structural vascular changes in angiotensinⅡ-treated rats[J]. Hypertens, 1998, 272(2): 77~84.
[32] Sun W, Wang L, Zhang Z, et al. Intramuscular transfer of naked calcitonin gene-related peptide gene prevents autoimmune diabetes induced by multiple low-dose streptozotocin in C57BL mice[J]. European Journal Immuno1ogy, 2003, 2(33): 233~242.
[33] Wei H M, Sinha A K, Weiss H R. Cervical sympathectomy reduces the heterogeneity of oxygen saturation in small cerebrocorucal veins[J]. Journal of Applied Physiology, 1993, 3(74): 1911~1915.
[34]刘树铮.低剂量电离辐射对某些免疫功能的影响[J].中华放射医学与防护杂志, 1987, 9(1): 8~11.
[35]鞠桂芝,宋春华,刘树铮.低剂量辐射诱发免疫适应性反应的剂量响应[J].中华放射医学与防护杂志.1994, 14(1): 15~17.
[36] Okamoto K. Critical Values of Linear Energy Transfer, Dose Rate and Doses for Radiation Hormesis[J]. Health Physics, 1987, 52(5): 671~674.
[37]刘树铮,肖佩新,马士盐等.广东天然放射性高本底地区居民细胞免疫的研究[J].中华放射医学与防护杂志, 1982, 2(3):64~67.
[38]刘树铮,徐桂珍,李修义等.广东天然放射性高本底地区居民免疫功能再研究[J].中华放射医学与防护杂志,1985, 5: 124~126.
[39] Annunziato F, CosmiL, Liotta F, et al. Phenotype, localization, and mechanism of suppression of CD4+CD25+human thymocytes[J]. The Journal of Experimental Medicine, 2002, 196(3):379~387.
[40] Cosmi L, Liotta F, Lazzeri E, et al. Human CD8+CD25+thymocytes share phenotypic and functional features with CD4+CD25+regulatory thymocytes[J]. Blood, 2003, 102(12): 4107~4114.
[41] Rao P E, Petrone A L, Ponath P D. Differentiation and expansion of T cells with regulatory function from human peripheral lymphocytes by stimulation in the presence of TGF-β[J]. Journal of Immunology, 2005, 174(3): 1446~1455.
[42] Charbonneau H, Tonks N K, Walsh K A. The leukocyte common antigen(CD45): a putative receptor-linked protein tyrosine phosphatase[J]. The Proceedings of National Academy of Science Usa, 1998, 85(19):7182~7186.
[43] Uzawa A, Suzuki G, Nakata Y, et al. Radiosensitivity of CD45 RO+ memory and CD45 RO- naive T cells in culture[J]. Radiation Research, 1994, 137(5): 25~27.
[44]涂开成,曹珍山,叶常青.急性放射病照后不同时间淋巴细胞和白细胞数与受照剂量的定量关系[J].中华放射医学与防护杂志, 1996, 16(2): 115~117.
[45]张爱梅,翟志敏,徐修才等.标本放置时间及年龄对CD4+CD25+调节性T细胞的影响[J].免疫学杂志, 2007, 23: 62~65.
[46] Vizi E S, Orso E, Osipenko O N, et a1. Neurochemical, electrophysiological and immunocytochemical evidence for a noradrenergic link between the sympathetic nervous system and thymocytes[J]. Neuroscience, 1995, 68(4): 1263~1276.
[47] Madden KS, Felten SY, Felten DL, et al. Sympathetic nervous system modulation of the immune system. II. Induction of lymphocyte proliferation and migration in vivo by chemical sympathectomy[J]. Journal of Neuroimmunology, 1994, 49(1): 67~75.
[48]夏寿萱.放射生物学[M].北京:军事医学科学出版社, 1998. 472~475.
[49] Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases[J]. Journal of Immunology, 1995, 155(3): 1151~1164.
[50]李健,张艮甫. CD4+CD25+调节性T细胞诱导移植免疫耐受研究进展[J].内分泌外科杂志2007, 1(4): 268~270.
[51]王卫文,张戎,杨晓帆等.正常人外周血中CD8+CD25+T细胞亚群的数量及其细胞因子表达的初步研究[J].南京医科大学学报(自然科学版), 2007, 27(10): 1092~1097.
[52] Kelley S Madden, Suzanne Y Stevens, David L Felten, et al. Alterations in T lymphocyte activityfollowing chemical sympathectomy in young and old Fischer 344 rats[J]. Journal of Neuroimmunology, 2000, 103(1): 131~145.
[53] Crolmpton NEA, Pzsahin M. A versatile and rapid assay of radiosensitivity of peripheral blood leukocytes based on DNA and surface-marker assessment of cytotoxicity[J]. Radiation Research, 1997, 147(1): 55~60.
[54] Luckey T D. Hormesis with ionizing radiation[M]. Boca Raton, CRC Press, 1980: 101~104.
[55] Saito H. The relationship between the sympathetic nerves and immunocytes in the spleen[J]. Kaibogaku Zasshi, 1991, 66: 8~19.
[56] Mary D, Peyron J F, Auberger P, et al. Modulation of T cell activation by differential regulation of the phosphorylation of two cytosolic proteins[J]. Journal of Biological Chemistry, 1989, 264(24): 14498~14502.
[57] Chen D, Rothenberg E V. Interleukin 2 transcription factors as molecular targets of cAMP inhibition: delayed inhibition kinetics and combinatorial transcription roles[J]. Journal of Experimental Medicine, 1994, 179(3): 931~942.
[58] Tamir A, Isakov N. Cyclic AMP inhibits phosphatidylinositolcoupled and -uncoupled mitogenic signals in T lymphocytes. Evidence that cAMP alters PKC-induced transcription regulation of members of the jun and fos family of genes[J]. Journal of Immunology, 1994, 152(7): 3391~3399.
[59] Feldman R D, Hunninghake G W, McArdle W. Beta-Adrenergic receptor-mediated suppression of interleukin 2 receptors in human lymphocytes[J]. Journal of Immunology, 1987, 139(10): 3355~3359.
[60] Krause D S, Deutsch C. Cyclic AMP directly inhibits IL-2 receptor expression in human T cells: expression of both p55 and p75 subunits is affected[J]. Journal of Immunology, 1991, 146(7), 2285~2294.
[61] Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes autoimmune diseases[J]. Journal of Immunology, 1995, 155(3): 1151~1164.
[62] Glaser R. Stress-associated immune dysregulation and its importance for human health: a personal history of psychoneuroimmunology[J]. Brain, Behavior and Immunity, 2005, 19(1):3~11.
[63] Heijnen C.J., Cohen N. Clinical significance of the neuroendocrine control of autoimmune processes: a important niche for psychoneuroimmunologists[J]? Brain, Behavior and Immunity, 1999, 13(4): 267~270.
[2] Adam P, Kohm, Virginia M. Sanders. Norepinephrine: a messenger from the brain to the immune system[J]. Immunology Today, 2000, 21(11): 539~542.
[3] Sternberg E M. Neural-immune interactions in health and disease[J]. Annals of New York Academy of Sciences, 1997, 100(11): 20~27.
[4] Straub R H. Complexity of the bi-directional neuroimmune junction in the spleen[J]. Trends in Pharmacological Sciences, 2004, 25(12): 640~646.
[5] Brogden K A, Guthmiller J M, Salzet M, et al. The nervous system and innate immunity: the neuropeptide connection[J]. Nature Immunology, 2005, 6(6): 558~564.
[6] Webster J I, Tonelli L, Sternberg EM. Neuroendocrine regulation of immunity[J]. Annual Review of Immunology, 2002, 20:125~163.
[7] Delgado M, Pozo D, Ganea D. The significance of vasoactive intestinal peptide in immunomodulation[J]. Pharmacologcial Reviews, 2004, 56(2):249~290.
[8] Bulloch K, Moore R Y. Innervation of the thymus gland by brain stem and spinal cord in mouse and rat[J]. American Journal of Anatomy, 1981, 162(2): 157~166.
[9] Bulloch K, Pomerantz W. Autonomic nervous system innervation of thymic related lymphoid tissue in wild-type and nude mice[J]. Journal of Comparative Neurology, 1984, 228(1): 57~68.
[10] Nance D M, Hopkins D A, Bieger D. Re-investigation of the innervation of the thymus gland in mice and rats[J]. Brain, Behavior and Immunology, 1987, 1(2): 134~147.
[11] Nicholas Trotter, Ruth L Stornetta. Transneuronal mapping of the CNS network controlling sympathetic outflow to the rat thymus[J]. Autonomic Neuroscience: Basic and Clinical, 2007, 131(1-2): 9~20.
[12] Wan W, Wetmore L, Sorensen C M, et al. Neural and biochemical mediators of endotoxin and stress-induced c-fos expression in the rat brain[J]. Brain Research Bulletin., 1994. 34(1): 7~14.
[13] Nance D M, Burns J. Innervation of the spleen in the rat: evidence for absence of afferent innervation[J]. Brain, Behavior and Immunology, 1989, 3(4): 281~290.
[14] Bellinger D L, Lorton D, Hamill R W, et al. Acetylcholinesterase staining and choline acetyltransferase activity in the young adult rat spleen: lack of evidence for cholinergicinnervation[J]. Brain, Behavior and Immunology, 1993, 7(3): 191~204.
[15] Schafer M K., Eiden L E, Weihe E. Cholinergic neurons and terminal fields revealed by immunohistochemistry for the vesicular acetylcholine transporter. II. The peripheral nervous system[J]. Neuroscience, 1998, 84(2): 361~376.
[16] Cano G, Sved A F, Rinaman L, et al. Characterization of the central nervous system innervation of the rat spleen using viral transneuronal tracing[J]. Journal of Comparative Neurology, 2001, 439(1): 1~18.
[17] Nicholas W K, Virginia M S. It takes nerve to tell T and B cells what to do[J]. Journal of Leukocyte Biology, 2006, 79: 1093~1104.
[18] Sanders V M, Kasprowicz D J, Kohm A P, et al. Neurotransmitter receptors on lymphocytes and other lymphoid cells, third ed[M]. In: Ader, R., Felten, D., Cohen, N. (Eds.) Psychoneuro -immunology, 2001, 2: 161~196.
[19] Kavelaars A. Regulated expression of alpha-1 adrenergic receptors in the immune system[J]. Brain Behav. Immun., 2002, 16(6): 799~807.
[20] Ignatowski T A, Gallant S., Spengler R.N. Temporal regulation by adrenergic receptor stimulation of macrophage (M phi)-derived tumor necrosis factor (TNF) production post LPS challenge[J]. Journal of Neuroimmunology, 1996, 65(2): 107~117.
[21] Meltzer J C, MacNeil B J, Sanders V., et al. Stress-induced suppression of in vivo splenic cytokine production in the rat by neural and hormonal mechanisms[J]. Brain, Behavior and Immunology, 2004, 18(3): 262~273.
[22] Sanders V M, Munson A E. Norepinephrine and the antibody response[J]. Pharmacologcial Reviews, 1985, 37(3): 229~248.
[23] Sanders V M, Kasprowicz D J, Swanson-Mungerson M A, et al. Adaptive immunity in mice lacking the beta2-adrenergic receptor[J]. Brain, Behavior and Immunology, 2003, 17(1): 55~67.
[24] Kohm A P, Sanders V M. Norepinephrine and beta2-adrenergic receptor stimulation regulate CD4+T and B lymphocyte function in vitro and in vivo[J]. Pharmacological Reviews, 2001b, 53(4):487~525.
[25] Madden K S, Felten S Y, Felten D L, et al. Sympathetic neural modulation of the immune system. I. Depression of T cell immunity in vivo and in vitro following chemical sympathectomy[J]. Brain, Behavior and Immunology, 1989, 3(1): 72~89.
[26] Callahan T A, Moynihan J A. The effects of chemical sympathectomy on T-cell cytokine responses are not mediated by altered peritoneal exudate cell function or an inflammatoryresponse[J]. Brain, Behavior and Immunology, 2002, 16(1): 33~45.
[27] Alaniz R C, Thomas S A, Perez-Melgosa M., et al. Dopamine beta-hydroxylase deficiency impairs cellular immunity[J]. The Proceedings of National Academy of Science Usa, 1999, 96(5): 2274~2278.
[28] Kohm A P, Sanders V M. Norepinehrine and beta-2-adrenergic receptor stimulation regulate CD4+T and B lymphocyte function in vitro and in vivo[J]. Pharmacological Reviews, 2001a, 53(3): 487~525.
[29] Sanders V M, Straub R H. Norepinephrine, the beta-adrenergic receptor, and immunity[J]. Brain, Behavior and Immunology, 2002, 16(4): 290~332.
[30] Pongratz G., McAlees J W, Conrad D H, et al. The level of IgE produced by a B Cell is regulated by norepinephrine in a p38 MAPK- and CD23-dependent manner[J]. Journal of Immunology, 2006, 177(5): 2926~2938.
[31] Simon C, Csiky B. Effect of neonatal sympathectomy on the development of structural vascular changes in angiotensinⅡ-treated rats[J]. Hypertens, 1998, 272(2): 77~84.
[32] Sun W, Wang L, Zhang Z, et al. Intramuscular transfer of naked calcitonin gene-related peptide gene prevents autoimmune diabetes induced by multiple low-dose streptozotocin in C57BL mice[J]. European Journal Immuno1ogy, 2003, 2(33): 233~242.
[33] Wei H M, Sinha A K, Weiss H R. Cervical sympathectomy reduces the heterogeneity of oxygen saturation in small cerebrocorucal veins[J]. Journal of Applied Physiology, 1993, 3(74): 1911~1915.
[34]刘树铮.低剂量电离辐射对某些免疫功能的影响[J].中华放射医学与防护杂志, 1987, 9(1): 8~11.
[35]鞠桂芝,宋春华,刘树铮.低剂量辐射诱发免疫适应性反应的剂量响应[J].中华放射医学与防护杂志.1994, 14(1): 15~17.
[36] Okamoto K. Critical Values of Linear Energy Transfer, Dose Rate and Doses for Radiation Hormesis[J]. Health Physics, 1987, 52(5): 671~674.
[37]刘树铮,肖佩新,马士盐等.广东天然放射性高本底地区居民细胞免疫的研究[J].中华放射医学与防护杂志, 1982, 2(3):64~67.
[38]刘树铮,徐桂珍,李修义等.广东天然放射性高本底地区居民免疫功能再研究[J].中华放射医学与防护杂志,1985, 5: 124~126.
[39] Annunziato F, CosmiL, Liotta F, et al. Phenotype, localization, and mechanism of suppression of CD4+CD25+human thymocytes[J]. The Journal of Experimental Medicine, 2002, 196(3):379~387.
[40] Cosmi L, Liotta F, Lazzeri E, et al. Human CD8+CD25+thymocytes share phenotypic and functional features with CD4+CD25+regulatory thymocytes[J]. Blood, 2003, 102(12): 4107~4114.
[41] Rao P E, Petrone A L, Ponath P D. Differentiation and expansion of T cells with regulatory function from human peripheral lymphocytes by stimulation in the presence of TGF-β[J]. Journal of Immunology, 2005, 174(3): 1446~1455.
[42] Charbonneau H, Tonks N K, Walsh K A. The leukocyte common antigen(CD45): a putative receptor-linked protein tyrosine phosphatase[J]. The Proceedings of National Academy of Science Usa, 1998, 85(19):7182~7186.
[43] Uzawa A, Suzuki G, Nakata Y, et al. Radiosensitivity of CD45 RO+ memory and CD45 RO- naive T cells in culture[J]. Radiation Research, 1994, 137(5): 25~27.
[44]涂开成,曹珍山,叶常青.急性放射病照后不同时间淋巴细胞和白细胞数与受照剂量的定量关系[J].中华放射医学与防护杂志, 1996, 16(2): 115~117.
[45]张爱梅,翟志敏,徐修才等.标本放置时间及年龄对CD4+CD25+调节性T细胞的影响[J].免疫学杂志, 2007, 23: 62~65.
[46] Vizi E S, Orso E, Osipenko O N, et a1. Neurochemical, electrophysiological and immunocytochemical evidence for a noradrenergic link between the sympathetic nervous system and thymocytes[J]. Neuroscience, 1995, 68(4): 1263~1276.
[47] Madden KS, Felten SY, Felten DL, et al. Sympathetic nervous system modulation of the immune system. II. Induction of lymphocyte proliferation and migration in vivo by chemical sympathectomy[J]. Journal of Neuroimmunology, 1994, 49(1): 67~75.
[48]夏寿萱.放射生物学[M].北京:军事医学科学出版社, 1998. 472~475.
[49] Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases[J]. Journal of Immunology, 1995, 155(3): 1151~1164.
[50]李健,张艮甫. CD4+CD25+调节性T细胞诱导移植免疫耐受研究进展[J].内分泌外科杂志2007, 1(4): 268~270.
[51]王卫文,张戎,杨晓帆等.正常人外周血中CD8+CD25+T细胞亚群的数量及其细胞因子表达的初步研究[J].南京医科大学学报(自然科学版), 2007, 27(10): 1092~1097.
[52] Kelley S Madden, Suzanne Y Stevens, David L Felten, et al. Alterations in T lymphocyte activityfollowing chemical sympathectomy in young and old Fischer 344 rats[J]. Journal of Neuroimmunology, 2000, 103(1): 131~145.
[53] Crolmpton NEA, Pzsahin M. A versatile and rapid assay of radiosensitivity of peripheral blood leukocytes based on DNA and surface-marker assessment of cytotoxicity[J]. Radiation Research, 1997, 147(1): 55~60.
[54] Luckey T D. Hormesis with ionizing radiation[M]. Boca Raton, CRC Press, 1980: 101~104.
[55] Saito H. The relationship between the sympathetic nerves and immunocytes in the spleen[J]. Kaibogaku Zasshi, 1991, 66: 8~19.
[56] Mary D, Peyron J F, Auberger P, et al. Modulation of T cell activation by differential regulation of the phosphorylation of two cytosolic proteins[J]. Journal of Biological Chemistry, 1989, 264(24): 14498~14502.
[57] Chen D, Rothenberg E V. Interleukin 2 transcription factors as molecular targets of cAMP inhibition: delayed inhibition kinetics and combinatorial transcription roles[J]. Journal of Experimental Medicine, 1994, 179(3): 931~942.
[58] Tamir A, Isakov N. Cyclic AMP inhibits phosphatidylinositolcoupled and -uncoupled mitogenic signals in T lymphocytes. Evidence that cAMP alters PKC-induced transcription regulation of members of the jun and fos family of genes[J]. Journal of Immunology, 1994, 152(7): 3391~3399.
[59] Feldman R D, Hunninghake G W, McArdle W. Beta-Adrenergic receptor-mediated suppression of interleukin 2 receptors in human lymphocytes[J]. Journal of Immunology, 1987, 139(10): 3355~3359.
[60] Krause D S, Deutsch C. Cyclic AMP directly inhibits IL-2 receptor expression in human T cells: expression of both p55 and p75 subunits is affected[J]. Journal of Immunology, 1991, 146(7), 2285~2294.
[61] Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes autoimmune diseases[J]. Journal of Immunology, 1995, 155(3): 1151~1164.
[62] Glaser R. Stress-associated immune dysregulation and its importance for human health: a personal history of psychoneuroimmunology[J]. Brain, Behavior and Immunity, 2005, 19(1):3~11.
[63] Heijnen C.J., Cohen N. Clinical significance of the neuroendocrine control of autoimmune processes: a important niche for psychoneuroimmunologists[J]? Brain, Behavior and Immunity, 1999, 13(4): 267~270.