NATURAL CELL-MEDIATED RESISTANCE IN CRYPTOCOCCOSIS

细胞及其参与天然细胞介导的抗病机制 新隐球菌类酵母菌的定义还不是很清楚。 正常未受刺激的动物体内有三种不同的细胞群 它们有可能清除组织中的隐球菌。这些是 中性粒细胞(PMNL)、巨噬细胞和自然杀伤细胞(NK) 细胞。在过去的三年里，我们研究了自然环境的影响 体内和体外对新生葡萄球菌的效应细胞。从这些 研究表明，正常小鼠的细胞中有 抗隐球菌活性，并通过众多标准，具有特点 匹配的NK细胞。尽管NK细胞不能杀灭 10/3隐球菌的培养并不能完全清除小鼠体内的新生隐球菌 感染了10/4的生物，它们确实显著减少了 两种情况下都是隐球菌。这些发现表明，NK细胞 与PMNL和巨噬细胞一起参与初始清除 寄主组织中的隐球菌。NK细胞通过一种途径影响新生葡萄球菌 非吞噬机制，包括NK细胞首先与 有机体随后抑制隐球菌的生长。《抒情》 细胞毒性T淋巴细胞(CTL)和自然杀伤细胞(NK细胞)对小鼠脾细胞的杀伤作用 组织靶点似乎是效应细胞胞吐的结果 含有细胞溶解成分的颗粒。我们正在提议一个类似的 其作用机制可能是NK细胞介导的抑制隐球菌 成长。然而，我们早期的研究表明，NK的动力学 细胞与隐球菌的结合和对隐球菌生长的抑制作用 比肿瘤细胞靶点要慢。这表明可能存在 NK细胞对隐球菌结合反应方式的差异 靶点与肿瘤细胞靶点以及在活性成分或手段中 NK细胞的活性成分通过什么影响酵母靶标。我们现在 建议进行调查，以基本了解NK的相互作用 带有隐球菌的细胞，这是一个与 此前曾研究过北韩的目标。要做到这一点，我们将确定顺序 抑制隐球菌生长的措施，研究其变化 发生在效应器和靶细胞中，在使用光和 电子显微镜技术，并评价有哪些特定成分(S) NK细胞具有抗隐球菌活性。这些研究 应该提供新的和重要的信息关于自然的 隐球菌病中细胞介导的耐药性。

Cells and mechanisms involved in natural cell mediated resistance against the yeast-like organism, Cryptococcus neoformans are not well defined. There are three different cell populations in normal unstimulated animals which have the potential to clear cryptococci from tissues. These are polymorphonuclear leukocytes (PMNL), macrophages, and natural killer (NK) cells. Over the past three years, we have studied the effects of natural effector cells on C. neoformans both in vivo and in vitro. From these studies, it is clear that normal mice have cells which have anti-Cryptococcus activity and by numerous criteria, have characteristics matching NK cells. Although NK cells are not capable of sterilizing a culture of 10/3 cryptococci nor totally eliminating C. neoformans from mice infected with 10/4 organisms, they do significantly reduce the numbers of cryptococci in both cases. These findings suggest that NK cells participate along with PMNL and macrophages in initial clearance of cryptococci from host tisuses. NK cells affect C. neoformans by a nonphagocytic mechanism which includes first binding of the NK cells to the organism then later inhibiting the growth of the cryptococci. The lytic effects of cytotoxic T lymphocytes (CTL) and NK cells against appropriate tissue targets appear to be the result of effector cell exocytosis of granules containing cytolytic components. We are proposing that a similar mechanism may be operating in NK cell mediated inhibition of cryptococci growth. However, our earlier studies have shown that the kinetics of NK cell binding to cryptococci and inhibition of cryptococci growth are much slower than with tumor cell targets. This suggests there may be differences in the way the NK cells respond to binding of cryptococci targets versus tumor cell targets and in the active components or the means by which active components of NK cells affect the yeast target. We now propose investigations to gain a basic understanding of interactions of NK cells with cryptococci, a target which is substantially different from previously studied NK targets. To do this we will determine the sequence of steps leading to inhibition of cryptococci growth, study the changes occurring in the effector and target cells after binding using light and electron microscopy techniques, and asses what specific component(s) of the NK cells is responsible for the anti-Cryptococcus activity. These studies should provide new and significant information on the mechanisms of natural cell mediated resistance in cryptococcosis.