Moran P A, Diegel M L, Sias J C, Ledbetter J A, Zarling J M
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
AIDS Res Hum Retroviruses. 1993 May;9(5):455-64. doi: 10.1089/aid.1993.9.455.
The relationship between production of HIV-1 by peripheral blood mononuclear cells (PBMCs) from HIV-1-infected donors and the level of T cell activation by various stimuli was examined. Stimulation of PBMCs with soluble anti-CD3 antibody or staphylococcal enterotoxin/superantigen (SAg) was found to be 100-1000 times more effective at inducing production of HIV-1 than was stimulation with immobilized anti-CD3 or various other T cell activating agents. However, proliferation of CD4+ T cells and lymphokine production following stimulation with soluble anti-CD3 were less than with immobilized anti-CD3. To determine whether immobilized anti-CD3 stimulated cells may produce a factor(s) that suppresses HIV production, dual-chamber coculture experiments were performed in which soluble and immobilized anti-CD3-stimulated CD8-depleted PBMCs were separated by porous membranes. Stimulation of cells by immobilized anti-CD3 suppressed HIV-1 production by soluble anti-CD3-stimulated cells in the inner chamber, suggesting that diffusible factor(s) are involved in suppressing HIV-1 production. Experiments in which exogenous cytokines were added to cells stimulated with soluble anti-CD3 did not reveal the suppressive factor(s) produced; however, IL-7 was found to markedly increase HIV-1 production. Both T cells and monocytes were found to be required for soluble anti-CD3 to induce high levels of HIV-1 production, suggesting a role for adhesion molecules. Our results thus show that (1) soluble anti-CD3 is a powerful stimulus for HIV production, (2) there is not an absolute correlation between the level of HIV-1 production and T cell activation following stimulation of PBMCs with T cell activating agents, (3) immobilized anti-CD3 stimulation produces a factor that decreases HIV replication, and (4) T cell monocyte interactions are important for production of HIV-1 following stimulation with soluble anti-CD3.
研究了来自HIV-1感染供体的外周血单核细胞（PBMC）产生HIV-1与各种刺激导致的T细胞活化水平之间的关系。发现用可溶性抗CD3抗体或葡萄球菌肠毒素/超抗原（SAg）刺激PBMC诱导HIV-1产生的效力比用固定化抗CD3或各种其他T细胞活化剂刺激高100 - 1000倍。然而，可溶性抗CD3刺激后CD4 + T细胞的增殖和淋巴因子产生低于固定化抗CD3刺激后的情况。为了确定固定化抗CD3刺激的细胞是否可能产生抑制HIV产生的因子，进行了双室共培养实验，其中可溶性和固定化抗CD3刺激的CD8缺失PBMC通过多孔膜分开。固定化抗CD3对细胞的刺激抑制了内腔中可溶性抗CD3刺激细胞的HIV-1产生，表明可溶性因子参与抑制HIV-1产生。在用可溶性抗CD3刺激的细胞中添加外源性细胞因子的实验未揭示所产生的抑制因子；然而，发现IL-7可显著增加HIV-1产生。发现可溶性抗CD3诱导高水平HIV-1产生需要T细胞和单核细胞两者，提示黏附分子起作用。因此，我们的结果表明：（1）可溶性抗CD3是HIV产生的有力刺激物；（2）用T细胞活化剂刺激PBMC后，HIV-1产生水平与T细胞活化之间不存在绝对相关性；（3）固定化抗CD3刺激产生一种可降低HIV复制的因子；（4）T细胞与单核细胞的相互作用对于可溶性抗CD3刺激后HIV-1的产生很重要。
