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人类淋巴细胞抑制新型隐球菌的机制。

Mechanisms of inhibition of Cryptococcus neoformans by human lymphocytes.

作者信息

Levitz S M, North E A, Dupont M P, Harrison T S

机构信息

Evans Memorial Department of Clinical Research, Boston University Medical Center Hospital, Massachusetts, USA.

出版信息

Infect Immun. 1995 Sep;63(9):3550-4. doi: 10.1128/iai.63.9.3550-3554.1995.

Abstract

Recently, our laboratory and others have demonstrated that human peripheral blood T and NK lymphocytes directly inhibit the growth of Cryptococcus neoformans. In this study, we further define the conditions under which lymphocyte-mediated fungistasis against C. neoformans occurs and examine whether mechanisms implicated in lymphocyte-mediated activities against other target cells are also involved in anticryptococcal activity. The addition of whole or broken heat-killed C. neoformans modestly inhibited lymphocyte-mediated fungistasis, whereas other particulates had no effect. The hydroxyl radical scavenger catechin, but not diethyl urea or propyl gallate, profoundly inhibited fungistasis. Salicylic acid inhibited fungistasis in a dose-dependent fashion. However, two other cyclooxygenase inhibitors, piroxicam and indomethacin, had no effect, suggesting that the mechanism of inhibition by salicylic acid was cyclooxygenase independent. Reagent prostaglandin E2, at concentrations shown by others to inhibit NK cell-mediated bactericidal and tumorlytic activities, had no effect on lymphocyte-mediated fungistasis. The addition of selected monoclonal antibodies or ligands reactive with receptors on human lymphocytes had no significant effect on lymphocyte-mediated fungistasis. Acapsular, small-capsuled, and large-capsuled C. neoformans organisms were inhibited by lymphocytes to an approximately equal extent. These data demonstrate that lymphocyte-mediated activity against C. neoformans proceeds regardless of the presence of capsule and by mechanisms at least in part dissimilar from those seen with other target cells.

摘要

最近,我们实验室及其他机构已证明,人类外周血T淋巴细胞和NK淋巴细胞可直接抑制新型隐球菌的生长。在本研究中,我们进一步明确了淋巴细胞介导的针对新型隐球菌的抑菌作用发生的条件,并研究了与淋巴细胞介导的针对其他靶细胞的活性相关的机制是否也参与抗新型隐球菌活性。添加完整或破碎的热灭活新型隐球菌可适度抑制淋巴细胞介导的抑菌作用,而其他颗粒则无影响。羟基自由基清除剂儿茶素可显著抑制抑菌作用,而二乙脲或没食子酸丙酯则无此作用。水杨酸以剂量依赖的方式抑制抑菌作用。然而,另外两种环氧化酶抑制剂吡罗昔康和吲哚美辛则无作用,这表明水杨酸的抑制机制不依赖于环氧化酶。试剂前列腺素E2在其他研究显示可抑制NK细胞介导的杀菌和溶瘤活性的浓度下,对淋巴细胞介导的抑菌作用无影响。添加与人类淋巴细胞上的受体反应的选定单克隆抗体或配体对淋巴细胞介导的抑菌作用无显著影响。无荚膜、小荚膜和大荚膜的新型隐球菌菌株被淋巴细胞抑制的程度大致相同。这些数据表明,淋巴细胞介导的针对新型隐球菌的活性不受荚膜存在与否的影响,其机制至少部分不同于针对其他靶细胞的机制。

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