Wang Jian-Hua, Kwas Constance, Wu Li
Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
J Virol. 2009 May;83(9):4195-204. doi: 10.1128/JVI.00006-09. Epub 2009 Feb 11.
Dendritic cells (DCs) play a critical role in cell-to-cell-mediated transmission of human immunodeficiency virus type 1 (HIV-1). Interactions between intercellular adhesion molecules (ICAMs) and their ligands facilitate DC-T-cell contact. The interaction between ICAM-1 on DCs and leukocyte function-associated molecule 1 (LFA-1) on CD4(+) T cells has been proposed to be important for DC-mediated HIV-1 transmission. Given that DCs and T cells express multiple ICAMs and binding ligands, the relative importance of ICAMs in DC-mediated HIV-1 transmission remains to be defined. Here, we examine the role of ICAM-1, -2, and -3 in DC-mediated HIV-1 transmission to various types of target cells including primary CD4(+) T cells. The expression levels of ICAMs and their ligands on immature and mature DCs and various types of HIV-1 target cells were measured by flow cytometry. Blocking ICAM-1 in DCs with specific monoclonal antibodies and small interfering RNA impaired DC-mediated HIV-1 transmission. DC-mediated viral transmission was significantly inhibited when both ICAM-1 on DCs and LFA-1 on CD4(+) T cells were blocked. However, blockade of ICAM-1 on target cells did not significantly inhibit DC-mediated HIV-1 transmission. Ectopic expression and antibody blocking suggest that DC-mediated HIV-1 transmission to primary CD4(+) T cells is independent of ICAM-2 and ICAM-3. Taken together, our data clarified the role of ICAMs in DC-mediated HIV-1 transmission to CD4(+) T cells.
树突状细胞（DCs）在1型人类免疫缺陷病毒（HIV-1）的细胞间介导传播中起关键作用。细胞间黏附分子（ICAMs）与其配体之间的相互作用促进了DC与T细胞的接触。DC上的ICAM-1与CD4(+) T细胞上的白细胞功能相关分子1（LFA-1）之间的相互作用被认为对DC介导的HIV-1传播很重要。鉴于DC和T细胞表达多种ICAMs和结合配体，ICAMs在DC介导的HIV-1传播中的相对重要性仍有待确定。在此，我们研究了ICAM-1、-2和-3在DC介导的HIV-1向包括原代CD4(+) T细胞在内的各种类型靶细胞传播中的作用。通过流式细胞术测量未成熟和成熟DC以及各种类型HIV-1靶细胞上ICAMs及其配体的表达水平。用特异性单克隆抗体和小干扰RNA阻断DC中的ICAM-1会损害DC介导的HIV-1传播。当DC上的ICAM-1和CD4(+) T细胞上的LFA-1都被阻断时，DC介导的病毒传播受到显著抑制。然而，阻断靶细胞上的ICAM-1并没有显著抑制DC介导的HIV-1传播。异位表达和抗体阻断表明，DC介导的HIV-1向原代CD4(+) T细胞的传播独立于ICAM-2和ICAM-3。综上所述，我们的数据阐明了ICAMs在DC介导的HIV-1向CD4(+) T细胞传播中的作用。
