STRESSOR-INDUCED MODULATION OF ANTIGEN SPECIFIC IMMUNITY

厌恶性应激改变大鼠的细胞和体液免疫指标， 小鼠 使用暴露于急性（一次性）足电击应激源的大鼠， 霍乱毒素（CT）作为抗原，初步数据已导致的结论 （i）抗原特异性体外记忆脾细胞增殖和 血清抗体水平只有在初次免疫时才受到抑制， 应激后立即发生（但不超过24小时后）;（ii） 免疫后7天抗原致敏大鼠的应激源暴露 导致增强的抗原特异性脾细胞记忆增殖， 但抑制非特异性促分裂原诱导的增殖。 追求 这些应激诱导效应的免疫学机制， 拟进行的实验之一是研究辅助细胞 功能和T细胞对抗原的反应性 exposure. 由于对CT的免疫反应只有在足部电击时才会改变， 与免疫密切相关，应激可改变辅助细胞 功能 因此，具体目标1将解决急性 （i）通过抗原呈递细胞（APC）的抗原呈递的足电击， 和（ii）巨噬细胞（Mo）产生IL-1、IL-6、TNF、TGF和PGE 2。 此外，在体内的作用，钼在介导应激诱导的 抑制淋巴细胞功能，将进行研究。 具体目标 2将检查应激对T淋巴细胞对抗原的反应性的影响 在应激源暴露后立即进行。 因此，未引发的脾T细胞将 测定（i）对抗原特异性和非抗原特异性的增殖活性， 体外特异性信号，（ii）Th 1 CD 4 + T细胞的 分泌IL-2和IFN-γ，以及Th 2 CD 4 + T细胞以产生IL-4， IL-6，和（iii）CD 4+和CD 8 + T细胞辅助和抑制调节 功能，分别。 这些措施代表了主要的相互作用 T淋巴细胞抗原特异性免疫反应的组成部分，可以 也调节B细胞功能，如上所述， 在免疫接种时发生足震。 细胞增殖、细胞因子和 T细胞反应性的调节措施也将形成 《特定目标3》中的最后一系列调查员。 这些实验将 测试急性足部电击是否会不同程度地改变 初始和记忆T细胞对抗原特异性和非特异性信号的反应。 这将通过将脾T淋巴细胞从 应激和非应激抗原致敏的大鼠，进入OX-22-（记忆）和 OX-22+（未处理）人群，并评估在 具体目标2。 总的来说，这些研究将产生重要的 研究急性炎症改变的基本免疫机制的途径 压力源暴露，并促进了解环境如何 压力等因素会影响对病毒的免疫反应， 感染，如艾滋病毒。

Aversive stressors alter cellular and humoral immune measures in rats and mice. Using rats exposed to an acute (one time) footshock stressor, a cholera toxin (CT) as antigen, preliminary data has led to the conclusion that (i) antigen-specific in vitro memory spleen cell proliferation and serum antibody levels are suppressed only when primary immunization occurs immediately after the stressor (but not > 24 hrs later); (ii) stressor exposure of antigen-primed rats 7 days after immunization results in enhanced antigen-specific spleen cell memory proliferation, but suppressed non-specific mitogen-induced proliferation. In pursuing the immunological mechanisms of these stressor-induced effects, the focus of the proposed experiments will be on the study of accessory cell function and T cell reactivity to antigen immediately following stressor exposure. Since the immune response to CT is altered only when footshock is in close proximity to immunization, stress may alter accessory cell function. Therefore, Specific aim 1 will address the effects of acute footshock on (i) antigen presentation by antigen-presenting cells (APC), and (ii) macrophage (Mo) production of IL-1, IL-6, TNF, TGF, and PGE2. In addition, the in vivo role of Mo in mediating stressor-induced suppression of lymphocyte function, will be investigated. Specific aim 2 will examine the effect of stress on T lymphocyte reactivity to antigen immediately after stressor exposure. Thus, unprimed splenic T cells will be assayed for (i) proliferative activity to antigen-specific and non- specific signals in vitro, (ii) the ability of Th1 CD4+ T cells to secrete IL-2 and IFN-gamma, and Th2 CD4+ T cells to elaborate IL-4 and IL-6, and (iii) CD4+ and CD8+ T cell helper and suppressor regulatory function, respectively. These measures represent the major interacting components of T lymphocyte antigen-specific immune responses, that can also regulate B cell function, which, as stated above, was suppressed by footshock at the time of immunization. The proliferative, cytokine, and regulatory measures for T cell reactivity will also form the basis of the final series of investigators in Specific Aim 3. These experiments will test whether acute footshock differentially alters the reactivity of naive and memory T cells to antigen-specific and non-specific signals. This will be accomplished by dividing splenic T lymphocytes, from stressed and non-stressed antigen-primed rats, into OX-22- (memory) and OX-22+ (naive) populations, and assessing the parameters studied in Specific Aim 2. Collectively, these studies will generate important avenues for the investigation of basic immune mechanisms altered by acute stressor exposure, and facilitate understanding of how environmental factors, such as stress, can influence the immune response to viral infections, such as HIV.