ENCAPSULATION OF CRYPTOCOCCUS-NEOFORMANS IMPAIRS ANTIGEN-SPECIFIC T-CELL RESPONSES

ENCAPSULATION OF CRYPTOCOCCUS-NEOFORMANS IMPAIRS ANTIGEN-SPECIFIC T-CELL RESPONSES
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DOI:
10.1128/iai.59.11.3883-3888.1991
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发表时间:
1991-11-01
影响因子:
3.1
通讯作者:
BANCROFT, GJ
BANCROFT, GJ
中科院分区:
医学2区
文献类型:
--
作者:
COLLINS, HL;BANCROFT, GJ

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封装的酵母新型隐球菌是细胞介导免疫受损的患者机会性感染的重要原因。 该生物体的主要毒力决定因素是进入宿主后合成的抗吞噬多糖胶囊。 使用封装的强毒菌株和无荚膜无毒突变体,我们证明了封装菌株在体外刺激特异性 T 细胞反应的能力降低。 这种减少是由荚膜的抗吞噬作用介导的,而不是通过直接抑制抗原加工和呈递来介导,因为之前用补体进行的调理作用增强了纯化的抗原呈递细胞对封装的酵母细胞的摄取,并允许显着的 T 细胞激活。 一旦摄入,隐球菌就会通过氯喹敏感途径被激活的巨噬细胞有效处理。 隐球菌抗原在与巨噬细胞相互作用后 1 至 2 小时内即可被 T 细胞识别,并以主要组织相容性复合物限制的方式呈现。 我们的结果表明,多糖胶囊的抗吞噬作用是针对新型隐球菌的 T 细胞免疫发展的重要决定因素。
The encapsulated yeast Cryptococcus neoformans is a significant cause of opportunistic infection in patients with impaired cell-mediated immunity. The major virulence determinant of the organism is an antiphagocytic polysaccharide capsule synthesized after entry into the host. Using both an encapsulated virulent strain and an acapsular avirulent mutant, we have demonstrated the reduced ability of the encapsulated strain to stimulate specific T-cell responses in vitro. This reduction was mediated by the antiphagocytic action of the capsule rather than by direct inhibition of antigen processing and presentation, since prior opsonization with complement enhanced the ingestion of encapsulated yeast cells by purified antigen-presenting cells and allowed significant T-cell activation. Once ingestion had occurred, cryptococci were efficiently processed by activated macrophages via a chloroquine-sensitive pathway. Cryptococcal antigens were available for T-cell recognition within 1 to 2 h of interaction with macrophages and presented in a major histocompatibility complex-restricted manner. Our results suggest that the antiphagocytic action of the polysaccharide capsule is an important determinant for the development of T-cell immunity to C. neoformans.