IMMUNOSUPPRESSANTS AND LYMPHOCYTE FUNCTION

在过去的一年里，我们的主要精力集中在体外 艾滋病患者T淋巴细胞的反应性。 对于这些研究，我们有 采用T集落测定法。 迄今为止，我们的数据表明， 在这种综合征中菌落形成明显减少， 流行病学相关疾病ARC（艾滋病相关综合征）， 有些病人是艾滋病的前驱期。 T细胞集落生长失败 与T细胞的其他几个参数没有密切相关 免疫力 此外，还表明外源性IL-2能够 使大多数ARC综合征患者的殖民地生长正常化。 虽然艾滋病患者的克隆反应显著增加， 大多数的反应性仍显著低于对照。 这 与活化细胞上IL-2受体表达减少相关 淋巴细胞目前对艾滋病的研究关注：（1） 分离的T细胞亚群;（2）其他免疫调节剂的作用 包括IL-1、干扰素和重组IL-2;和（3）抑制因子 艾滋病患者细胞和血清对正常人淋巴细胞克隆生长的影响 细胞 在另一项使用T集落测定的研究中，两种化合物的抑制活性分别为： 常用的免疫抑制剂，环孢素和皮质类固醇， 广泛评价。 两种药物均引起剂量相关的抑制， 克隆生长 外源性IL-2可逆转激素的作用， 而不是IL-1。 相比之下，IL-2不能恢复处理细胞的反应性， 环孢菌素目前正在进行的其他研究正在评估 和细胞毒性免疫抑制剂的活性， 硫唑嘌呤、甲氨蝶呤和4-羟基环磷酰胺。 目前研究的第三阶段是针对控制因素的研究 正常T淋巴细胞集落生长。 分离的T细胞对PHA无反应; 然而，包含IL-1、IL-2或来自短期免疫的上清液， 几种肿瘤细胞系的培养物能够与 这种促分裂剂，来刺激克隆生长。 肿瘤细胞上清液 与IL-1或IL-2不同。 我们目前正在描述 这些活性上清液。 （IS）

During the past year, our prime concentration has been on the in vitro reactivity of T lymphocytes from AIDS patients. For these studies, we have employed the T-colony assay. Our data, to date, indicate that lymphocyte colony formation is markedly reduced in this syndrome and in the epidemiologically related disorder ARC (AIDS-related complex), which in some patients is a prodromal phase of AIDS. The failure to grow T colonies did not closely correlate with several other parameters of T-cell immunity. Furthermore, it was shown that exogenous IL-2 was able to normalize the colony growth of most patients with the ARC syndrome. Although clonal responses of AIDS patients was increased significantly, the reactivity of most was still considerably less than controls. This correlated with reduced expression of IL-2 receptors on activated lymphocytes. Current investigations in AIDS concern: (1) the reactivity of isolated T-cell subsets; (2) the effects of other immunomodulators including IL-1, interferon, and recombinant IL-2; and (3) the suppressor effects of cells and sera from AIDS patients on the clonal growth of normal cells. In another study using the T-colony assay, the inhibitory activities of two commonly used immunosuppressants, cyclosporin and corticosteroids, were extensively evaluated. Both drugs caused a dose-related inhibition of clonal growth. The effects of steroids were reversed by exogenous IL-2 but not IL-1. By contrast, IL-2 failed to restore reactivity of cells treated with cyclosporin. Additional studies now in progress are evaluating the activities of prostaglandins and cytotoxic immunosuppressants including azathioprine, methotrexate, and 4-hydroxycyclophosphamide. The third phase of current studies is directed at factors controlling normal T lymphocyte colony growth. Isolated T cells do not respond to PHA; however, inclusion of IL-1, IL-2, or supernatants derived from short-term cultures of several tumor cell lines are able to act, in conjunction with this mitogen, to stimulate clonal growth. The tumor cell supernatants appear distinct from either IL-1 or IL-2. We are currently characterizing these active supernatants. (IS)