Chougnet C, Cohen S S, Kawamura T, Landay A L, Kessler H A, Thomas E, Blauvelt A, Shearer G M
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
J Immunol. 1999 Aug 1;163(3):1666-73.
Dendritic cells (DC) are the most potent cells involved in the generation of primary and secondary immune responses. To assess the feasibility of using autologous DC as immunotherapy for HIV disease, we analyzed a variety of immune parameters using DC isolated from HIV-infected (HIV+) individuals, as well as DC obtained from HIV-uninfected (HIV-) individuals infected in vitro with HIV. After stimulation with recombinant CD40 ligand (CD40LT), cytokine and beta-chemokine production were similar by DC from HIV- donors infected in vitro with the CCR5-using HIV Ba-L strain (n = 8) compared with uninfected DC from the same donors. Production of beta-chemokines, but not of cytokines, was increased by a CXCR4-using IIIB strain-infected DC (n = 7). Stimulation of HIV-infected DC with CD40LT decreased infection in Ba-L-infected DC, but had no effect on IIIB-infected DC. Consistent with this finding, CD40LT down-regulated CCR5 and up-regulated CXCR4 expression on DC. Monocyte-derived DC were also propagated from 15 HIV+ and 13 HIV- donors. They exhibited similar expression of costimulatory molecules and produced similar amounts of IL-12, IL-10, and beta-chemokines, following stimulation. By contrast, stimulated PBMC from HIV+ patients exhibited decreased IL-12 and increased IL-10 production. In summary, phenotype, cytokine secretion, and beta-chemokine production by DC from HIV+ individuals were normal. These cells may prove useful in boosting cellular immune responses in HIV+ individuals.
树突状细胞（DC）是参与初次和二次免疫反应产生的最有效的细胞。为了评估使用自体DC作为HIV疾病免疫疗法的可行性，我们使用从HIV感染（HIV+）个体分离的DC以及从体外感染HIV的HIV未感染（HIV-）个体获得的DC分析了各种免疫参数。在用重组CD40配体（CD40LT）刺激后，与来自相同供体的未感染DC相比，用使用CCR5的HIV Ba-L株体外感染的HIV-供体的DC产生的细胞因子和β趋化因子相似（n = 8）。使用CXCR4的IIIB株感染的DC（n = 7）增加了β趋化因子的产生，但没有增加细胞因子的产生。用CD40LT刺激HIV感染的DC可降低Ba-L感染的DC中的感染，但对IIIB感染的DC没有影响。与此发现一致，CD40LT下调了DC上的CCR5并上调了CXCR4的表达。单核细胞衍生的DC也从15名HIV+和13名HIV-供体中增殖。刺激后，它们表现出相似的共刺激分子表达，并产生相似量的IL-12、IL-10和β趋化因子。相比之下，来自HIV+患者的受刺激PBMC表现出IL-12产生减少和IL-10产生增加。总之，HIV+个体的DC的表型、细胞因子分泌和β趋化因子产生是正常的。这些细胞可能被证明有助于增强HIV+个体的细胞免疫反应。
