Active lytic infection of human primary tonsillar B cells by KSHV and its noncytolytic control by activated CD4+ T cells
Active lytic infection of human primary tonsillar B cells by KSHV and its noncytolytic control by activated CD4+ T cells
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DOI：
10.1172/jci43755
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发表时间：
2011-03-01
影响因子：
15.9
通讯作者：
Ganem, Don
中科院分区：
文献类型：
--
作者：
Myoung, Jinjong;Ganem, Don
卡波西肉瘤相关疱疹病毒（KSHV）是一种B淋巴细胞病毒，其主要复制部位是口咽。KSHV可感染原代扁桃体外植体培养的T和B细胞。然而，T细胞不支持裂解性复制，而B细胞自发地产生大量的感染性病毒。在这里，我们提供了一种机制，激活的T细胞可能会促进或稳定潜伏期的KSHV感染B细胞的证据。当B细胞和活化T细胞的混合培养物暴露于KSHV时，观察到很少的自发病毒产生。从混合物中去除T细胞或用免疫抑制剂处理混合培养物可以增强病毒的产生。将活化的T细胞加回纯化的感染B细胞有效地抑制了KSHV的产生，这主要是由于CD 4（+）T细胞。这种抑制活性需要T细胞活化和直接细胞-细胞接触，但不需要事先暴露于KSHV抗原。抑制不是MHC限制性的，并且不导致靶细胞的杀伤。因此，我们提出，口咽T细胞激活的各种刺激可以识别受感染的靶B细胞的配体，导致信号传导事件，防止自发裂解激活，并促进潜伏感染，在这个隔间。
Kaposi sarcoma-associated herpesvirus (KSHV) is a B-lymphotropic virus whose primary site of replication is the oropharynx. KSHV can infect both T and B cells from primary tonsillar explant cultures. However, T cells do not support lytic replication, while B cells spontaneously produce substantial amounts of infectious virus. Here, we provide evidence for a mechanism by which activated T cells may promote or stabilize latency of KSHV infection in B cells. When mixed cultures of B cells and activated T cells were exposed to KSHV, little spontaneous virus production was observed. Removing T cells from the mix or treating the mixed culture with immune suppressants enhanced virus production. Adding back activated T cells to purified infected B cells efficiently suppressed KSHV production, primarily due to CD4(+) T cells. This suppressive activity required T cell activation and direct cell-cell contact, but not prior exposure to KSHV antigen. Suppression was not MHC restricted and did not result in killing of the target cell. We therefore propose that oropharyngeal T cells activated by a variety of stimuli can recognize ligands on infected target B cells, leading to signaling events that prevent spontaneous lytic activation and promote latent infection in this compartment.