Noninfectious X4 but not R5 human immunodeficiency virus type 1 virions inhibit humoral immune responses in human lymphoid tissue ex vivo.
Noninfectious X4 but not R5 human immunodeficiency virus type 1 virions inhibit humoral immune responses in human lymphoid tissue ex vivo.
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非感染性 X4（而非 R5）人类免疫缺陷病毒 1 型病毒颗粒会抑制离体人体淋巴组织中的体液免疫反应。
DOI：
10.1128/jvi.78.13.7061-7068.2004
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发表时间：
2004
影响因子：
5.4
通讯作者：
Margolis,LeonidB
中科院分区：
文献类型：
--
作者：
Fitzgerald,Wendy;Sylwester,AndrewW;Grivel,Jean-Charles;Lifson,JeffreyD;Margolis,LeonidB
人淋巴组织的离体人类免疫缺陷病毒1型（HIV-1）感染再现了体内HIV-1感染的某些方面，包括CD 4 +T细胞的严重耗竭和对回忆抗原或多克隆刺激的体液免疫应答的抑制。这些效应是由X4 HIV-1变体感染诱导的，而R5变体感染仅导致CD 4 +T细胞轻度耗竭，且不抑制免疫应答。为了研究在该离体系统中抑制免疫应答的机制，我们使用醛硫醇-2（AT-2）-灭活的病毒体，其具有功能性包膜糖蛋白，但不具有感染性，并且不消耗离体人淋巴组织中的CD 4 +T细胞。尽管如此，AT-2灭活的X4（而不是R5）HIV-1病毒粒子，即使只有短暂的暴露，也能抑制离体人淋巴组织中的抗体应答，与感染性病毒相似。这种现象由暴露于病毒的组织分泌的可溶性免疫抑制因子介导。
Ex vivo human immunodeficiency virus type 1 (HIV-1) infection of human lymphoid tissue recapitulates some aspects of in vivo HIV-1 infection, including a severe depletion of CD4+T cells and suppression of humoral immune responses to recall antigens or to polyclonal stimuli. These effects are induced by infection with X4 HIV-1 variants, whereas infection with R5 variants results in only mild depletion of CD4+T cells and no suppression of immune responses. To study the mechanisms of suppression of immune responses in this ex vivo system, we used aldrithiol-2 (AT-2)-inactivated virions that have functional envelope glycoproteins but are not infectious and do not deplete CD4+T cells in human lymphoid tissues ex vivo. Nevertheless, AT-2-inactivated X4 (but not R5) HIV-1 virions, even with only a brief exposure, inhibit antibody responses in human lymphoid tissue ex vivo, similarly to infectious virus. This phenomenon is mediated by soluble immunosuppressive factor(s) secreted by tissue exposed to virus.