MODULATION OF THE IMMUNE SYSTEM BY HYPERTHERMIA

在实验阶段，全身热疗(WBH) 而其他的热疗方式正在迅速发展，因为 治疗癌症的方法。有相当多的证据表明 表明温度升高会导致戏剧性的 免疫的各种成分和功能的变化 系统。我们已经证明了全身的生热微波 (WBTMW)暴露刺激巨噬细胞(MP)功能， 降低自然杀伤(NK)活性，抑制某些T细胞 人口。这些对WBTMW的不同免疫反应 暴露在空气中导致我们提出，温度升高会改变 宿主的一些基本免疫调节过程。我们 已经观察到WBTMW暴露显著增加了 B组原发(1级)和继发(2级)IgM反应 仓鼠和小鼠的SRBC细胞。我们将延长这些措施 WBH中1度和2度免疫球蛋白反应的研究与检测 以确定是否有任何能力的变化 B细胞进行Ig类转换。由于B细胞免疫球蛋白应答 受MP和T细胞以及NK细胞的调节，任何或所有 这些群体可能与观察到的WBTMW有关 对免疫球蛋白反应的影响。这项提案还将重点放在 旨在研究WBH诱导的可能性的实验 这些不同的分布和功能的调制 淋巴细胞和单核细胞。使用单克隆抗体来 T/H(Lyt 1)、T/S(Lyt 2)、NK(a-silo GM1)和B(Ig)细胞 结合荧光激活的流式细胞术，我们将 分析WBH和WBH脾中这些细胞的数量 对照组小鼠在SRBC免疫前后。免疫法 MP上的抗原表达同样可以定量。功能 这些细胞群体的变化将由细胞来量化 利用平移技术进行的耗尽和恢复实验 使用表面表型特异性单抗的技术。 对这些重组WBH/对照产生的B细胞反应 脾细胞将由米歇尔-达顿在体外进行测量 技术或体内通过在X-体内植入扩散腔- 受辐射的同基因小鼠。这些实验将从数量上 明确WBH治疗对T/H、T/S、MP、 PFC各时相的NK细胞和B细胞对SRBC的反应。这 提案代表了对潜力的第一次全面分析 WBH对免疫调节工作的影响并将提供 基线数据在WBH多通道设计中的应用 癌症治疗的方法。

While at the experimental stage, whole body hyperthermia (WBH) and other hyperthermia modalities are rapidly developing as methods of treating cancer. Considerable evidence has been generated showing that elevated temperature can cause dramatic changes on various components and functions of the immune system. We have shown that whole body thermogenic microwave (WBTMW) exposure stimulates macrophage (MP) functions, decreases natural killer (NK) activity, and depresses certain T cell populations. These diverse immune responses to WBTMW exposure leads us to propose that elevated temperature alters some fundamental immunoregulatory process(es) of the host. We have observed that WBTMW exposure markedly augments the primary (1 degree) and secondary (2 degree) IgM response of B cells to SRBC in both hamsters and mice. We will extend these studies and examine 1 degree and 2 degree IgG responses in WBH exposed mice to determine if there is any change in the ability of B cells to undergo Ig class switching. Since the B cell Ig response is regulated by MP and T cells, as well as NK cells, any or all of these populations could be implicated in the observed WBTMW effect on the Ig response. This proposal will also focus on experiments designed to examine the possibility of WBH-induced modulation of distribution and function of these various lymphocytes and monocytes. Employing monoclonal antibodies to T/H (Lyt 1), T/S (Lyt 2), NK (a-silo GM1) and B (Ig) cells in conjunction with fluorescense activated flow cytometry we will analyze the number of these cells in the spleens of WBH and control mice before and after immunization with SRBC. Ia antigen expression on MP can similarly be quantitated. Function changes in these cell populations will be quantitated by cell depletion and reconstitution experiments employing the panning technique with surface phenotypic specific monoclonal antibodies. B cell responses generated to these reconstituted WBH/control spleen cells will be measured in vitro by the Mishell Dutton technique or in vivo by implanting diffusion chambers into X- irradiated syngeneic mice. These experiments will quantitatively define potential influences of WBH treatment on T/H, T/S, MP, NK, and B cells on all phases of the PFC responses to SRBC. This proposal represents the first comprehensive analysis of potential WBH effects on the immunoregulatory work and will provide baseline data useful in the design of WBH multi-modality approaches to cancer treatment.