Shacklett Barbara L, Cox Catherine A, Wilkens David T, Karl Karlsson R, Nilsson Annelie, Nixon Douglas F, Price Richard W
Gladstone Institute of Virology and Immunology, University of California, San Francisco, California, USA.
J Infect Dis. 2004 Jun 15;189(12):2202-12. doi: 10.1086/421244. Epub 2004 May 24.
The central nervous system (CNS) is a recognized target for human immunodeficiency virus type 1 (HIV-1). CD8(+) T cells may mediate viral clearance from the CNS but also may contribute to immune-mediated neuronal damage.
Using 4- and 6-color flow cytometry, we investigated the role of adhesion molecules (very late antigen [VLA]-4 [ alpha 4 beta 1 integrin] and leukocyte function antigen [LFA]-1 [ alpha L beta 2 integrin]) and chemokine receptors (CXCR3 and CCR5) in CD8(+) T cell migration to cerebrospinal fluid (CSF) during HIV-1 infection.
CD8(+) T cells trafficking to CSF were uniformly VLA-4(high), LFA-1(high). CCR5 expression was significantly enhanced in T cells from CSF, compared with those from blood (P<.001), including HIV-1-specific CD8(+) T cells, and most T cells from CSF expressed both CXCR3 and CCR5. Interferon-inducible protein (IP)-10 (CXCL10) levels in CSF were significantly increased in HIV-1-positive individuals, relative to IP-10 levels in control subjects (P=.007), and a positive correlation was found between IP-10 levels and virus load in CSF (r2=.777; P=.0007).
These findings suggest that LFA-1, CCR5 and CXCR3, and IP-10 play an important role in lymphocyte trafficking to CSF during HIV-1 infection. These observations suggest a "push-pull" model, in which lymphocyte extravasation is driven by lymphocyte activation, expression of adhesion molecules, and increased vascular permeability and is coupled with chemokine-mediated trafficking to inflammatory sites in the CNS.
中枢神经系统（CNS）是公认的1型人类免疫缺陷病毒（HIV-1）的靶标。CD8(+) T细胞可能介导从CNS清除病毒，但也可能导致免疫介导的神经元损伤。
我们使用4色和6色流式细胞术，研究了黏附分子（极迟抗原[VLA]-4[α4β1整合素]和白细胞功能抗原[LFA]-1[αLβ2整合素]）和趋化因子受体（CXCR3和CCR5）在HIV-1感染期间CD8(+) T细胞迁移至脑脊液（CSF）中的作用。
迁移至CSF的CD8(+) T细胞均为VLA-4(高)、LFA-1(高)。与血液中的T细胞相比，CSF中T细胞的CCR5表达显著增强（P<0.001），包括HIV-1特异性CD8(+) T细胞，并且CSF中的大多数T细胞同时表达CXCR3和CCR5。相对于对照组受试者的IP-10水平，HIV-1阳性个体CSF中的干扰素诱导蛋白（IP）-10（CXCL10）水平显著升高（P = 0.007），并且在CSF中IP-10水平与病毒载量之间发现正相关（r2 = 0.777；P = 0.0007）。
这些发现表明，LFA-1、CCR5和CXCR3以及IP-10在HIV-1感染期间淋巴细胞向CSF的迁移中起重要作用。这些观察结果提示了一种“推拉”模型，其中淋巴细胞外渗由淋巴细胞活化、黏附分子表达和血管通透性增加驱动，并与趋化因子介导的向CNS炎症部位的迁移相关联。
