HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN GP120 PRODUCES IMMUNE DEFECTS IN CD4+ LYMPHOCYTES-T BY INHIBITING INTERLEUKIN-2 MESSENGER-RNA
HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN GP120 PRODUCES IMMUNE DEFECTS IN CD4+ LYMPHOCYTES-T BY INHIBITING INTERLEUKIN-2 MESSENGER-RNA
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DOI：
10.1073/pnas.87.6.2379
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发表时间：
1990-03-01
影响因子：
11.1
通讯作者：
PAHWA, S
中科院分区：
文献类型：
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作者：
OYAIZU, N;CHIRMULE, N;PAHWA, S
人类免疫缺陷病毒1型（HIV-1）的包膜糖蛋白gp 120已知抑制T细胞功能，但对这种免疫抑制的机制知之甚少。发现用可溶性gp 120预处理CD 4+破伤风类毒素特异性T细胞克隆对可溶性抗原驱动或抗CD 3单克隆抗体驱动的增殖反应、白细胞介素2（IL-2）产生和表面IL-2受体（IL-2 R）α链表达产生剂量依赖性抑制，所有这些都可通过加入外源性IL-2逆转。用gp 120处理抑制了编码IL-2的基因的mRNA，但不抑制IL-2 R基因的转录。旁路激活的T细胞克隆与佛波醇12-肉豆蔻酸酯13-乙酸加离子霉素不受gp 120预处理。因此，gp 120-CD 4相互作用干扰了CD 4分子在通过CD 3-抗原受体（Ti）复合物的信号转导中的重要作用。这种gp 120诱导的免疫抑制机制，如果在体内起作用，可能有助于抑制与HIV感染相关的特异性免疫反应。
Envelope glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1) is known to inhibit T-cell function, but little is known about the mechanisms of this immunosuppression. Pretreatment of a CD4+ tetanus toxoid-specific T-cell clone with soluble gp120 was found to exert a dose-dependent inhibition of soluble antigen-driven or anti-CD3 monoclonal antibody-driven proliferative response, interleukin 2 (IL-2) production, and surface IL-2 receptor (IL-2R) alpha-chain expression, all of which were reversed by the addition of exogenous IL-2. mRNA for the gene encoding IL-2 was suppressed by treatment with gp120, but IL-2R gene transcription was not inhibited. Bypass activation of the T-cell clone with phorbol 12-myristate 13-acetate plus ionomycin was unaffected by gp120 pretreatment. Thus, gp120-CD4 interaction interferes with an essential role of the CD4 molecule in signal transduction through the CD3-antigen receptor (Ti) complex. Such a mechanism of gp120-induced immunosuppression, if operative in vivo, could contribute to the depressed specific immune responses associated with HIV infection.