Human Immunodeficiency Virus Type 1 gp120 Reprogramming of CD4+ T-Cell Migration Provides a Mechanism for Lymphadenopathy
Human Immunodeficiency Virus Type 1 gp120 Reprogramming of CD4+ T-Cell Migration Provides a Mechanism for Lymphadenopathy
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DOI：
10.1128/jvi.00130-09
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发表时间：
2009-06-01
影响因子：
5.4
通讯作者：
Cruikshank, William W.
中科院分区：
文献类型：
--
作者：
Green, Daniel S.;Center, David M.;Cruikshank, William W.
人类免疫缺陷病毒1型（HIV-1）感染与外周血CD 4（+）T细胞减少和淋巴结病的发生有关。HIV-1诱导这些变化的确切机制尚未阐明。通过CCL 21介导的进入和鞘氨醇-1-磷酸（S1 P）介导的外出促进T细胞通过淋巴组织的运输。先前已经确定HIV-1包膜糖蛋白gp 120直接改变T细胞迁移，我们研究了在没有HIV-1感染的情况下gp 120是否可以影响CD 4（+）T细胞对参与T细胞通过淋巴组织运输的信号的反应。正常人T细胞与gp 120孵育1小时，通过增加对CCL 20和CCL 21的敏感性和完全抑制向S1 P的迁移，导致CD 4 T细胞迁移反应的重编程。在注射到NOD.CB17-Prkdc（scid）/J小鼠中之前，将人T细胞与gp 120孵育，导致CD 4（+）T细胞的淋巴结积聚增加，与未暴露于gp 120的T细胞相比，血液和脾脏中的CD 4（+）T细胞的积聚相应减少。gp 120的作用需要通过p56（lck）介导的CD 4信号传导。这些发现表明，gp 120单独可以改变CD 4（+）流入和流出淋巴结的方式与淋巴细胞减少症和淋巴结病的发展一致。
Infection by human immunodeficiency virus type 1 (HIV-1) is associated with decreases in peripheral CD4(+) T cells and development of lymphadenopathy. The precise mechanisms by which HIV-1 induces these changes have not been elucidated. T-cell trafficking through lymphoid tissues is facilitated by CCL21-mediated entry and sphingosine-1-phosphate (S1P)-mediated egress. Having previously determined that HIV-1 envelop glycoprotein, gp120, directly alters T-cell migration, we investigated whether gp120 without HIV-1 infection could influence the responses of CD4(+) T cells to the signals involved in T-cell trafficking through lymph tissue. Incubation of normal human T cells with gp120 for 1 h resulted in reprogramming of CD4 T-cell migratory responses by increasing sensitivity to CCL20 and CCL21 and complete inhibition of migration to S1P. Incubation of human T cells with gp120 prior to injection into NOD.CB17-Prkdc(scid)/J mice resulted in increases in lymph node accumulation of CD4(+) T cells, with reciprocal decreases in blood and spleen compared to T cells not exposed to gp120. The effects of gp120 required CD4 signaling mediated through p56(lck). These findings suggest that gp120 alone can alter CD4(+) influx and efflux from lymph nodes in a fashion consistent with the development of lymphopenia and lymphadenopathy.