Regulation of HIV production by blood mononuclear cells from HIV-infected donors: II. HIV-1 production depends on T cell-monocyte interaction.
Regulation of HIV production by blood mononuclear cells from HIV-infected donors: II. HIV-1 production depends on T cell-monocyte interaction.
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HIV 感染者的血液单核细胞产生 HIV 的调节：II。
DOI：
10.1089/aid.1993.9.465
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发表时间：
1993
影响因子：
1.5
通讯作者：
Ledbetter,JA
中科院分区：
文献类型：
--
作者：
Diegel,ML;Moran,PA;Gilliland,LK;Damle,NK;Hayden,MS;Zarling,JM;Ledbetter,JA
先前表明，某些可溶性抗 CD3 单克隆抗体 (MAb) 诱导的 T 细胞和单核细胞之间的细胞间相互作用是受感染供体的外周血单核细胞 (PBMC) 高水平产生 HIV-1 所必需的。葡萄球菌肠毒素或超抗原 (SAg) 是另一种诱导单核细胞与 T 细胞相互作用的有丝分裂原，可有效诱导 HIV-1 的产生。使用针对几种粘附分子的抗体来测试抗 CD3 或 SAg 激活后 HIV-1 产生中对 T 细胞和单核细胞相关粘附分子的需求。阻断 CD2-LFA-3 或 CD18-ICAM-1 可以抑制抗 CD3 或 SAg 诱导的 HIV-1 产生超过 90%，而不抑制 CD4+T 细胞增殖。当单克隆抗体将 T 细胞或单核细胞辅助受体与这些粘附分子结合时，可观察到 HIV 产生的抑制。通过可溶性 CTLA-4 融合蛋白（CD28 同源物）阻断 CD28-B7 相互作用，可抑制 HIV-1 产生和 CD4+T 细胞增殖。单克隆抗体对 CD2 和 CD18 的 HIV-1 抑制不需要 Fc 结合，因为这些单克隆抗体的 Fab 或 F(ab')2 片段可抑制 HIV-1 产生超过 80%。产生了针对 CD2 的嵌合单链 MAb，其含有与人 IgG1 (CD2 SFv-Ig) 恒定区连接的 MAb 35.1 至 CD2 的重链和轻链可变区。这种人源化 CD2 SFv-Ig 可抑制 HIV-1 产生 30% 至 >98%。因此，这些结果表明，患者 PBMC 产生 HIV 需要 T 细胞和单核细胞之间多种粘附途径的同时参与，并且可能对 HIV 感染的治疗具有影响。
Cell-cell interactions induced between T cells and monocytes by certain soluble anti-CD3 monoclonal antibodies (MAbs) were previously shown to be required for high-level production of HIV-1 by peripheral blood mononuclear cells (PBMCs) from infected donors. Staphylococcal enterotoxin or superantigen (SAg) is another mitogen inducing monocytes-T cell interactions that exhibit potent induction of HIV-1 production. Antibodies to several adhesion molecules were used to test the requirements for T cell- and monocyte-associated adhesion molecules in HIV-1 production following activation with anti-CD3 or SAg. Blocking of either CD2-LFA-3, or CD18-ICAM-1, inhibited anti-CD3-or SAg-induced HIV-1 production by more than 90% without inhibiting CD4+T cell proliferation. Inhibition of HIV production was observed when either the T cell or monocyte coreceptor was bound by MAbs to these adhesion molecules. Blocking of CD28-B7 interactions by soluble CTLA-4 fusion protein, a CD28 homolog, inhibited both HIV-1 production and CD4+T cell proliferation. Fc binding was not required for HIV-1 inhibition by MAbs to CD2 and CD18, because Fab or F(ab')2fragments of these MAbs inhibited HIV-1 production by more than 80%. A chimeric single-chain MAb to CD2 was produced, containing heavy and light chain variable regions from MAb 35.1 to CD2 linked to the constant regions of human IgG1(CD2 SFv-Ig). This humanized CD2 SFv-Ig inhibited HIV-1 production by 30% to >98%. These results thus indicate that simultaneous engagement of multiple adhesion pathways between T cells and monocytes are required for HIV production by patients PBMCs and may have implications for therapy of HIV infections.