Miller S B, Tse H, Rosenspire A J, King S R
Department of Biological Sciences, Wayne State University, Detroit, Michigan 48201.
Virology. 1992 Dec;191(2):973-7. doi: 10.1016/0042-6822(92)90275-t.
The cytopathic effects of HIV-1 produced by direct infection of human T cells do not account for the disproportionate loss of CD4-positive lymphocytes during the course of HIV infection. Previous studies have demonstrated the inhibition of uninfected human T cell activation and proliferation by the HIV-1 envelope glycoproteins, presumably due to gp120-CD4 interactions. To examine the ability of HIV-1 to inhibit T cell proliferation in the absence of both direct infection and gp120-CD4 interactions, we tested the effect of HIV-1 on mouse T cell proliferation. Culture media containing HIV-1 released from infected cells inhibited T lymphocyte proliferation in response to interleukin-2 (IL-2). Studies to explore the mechanism of this inhibition suggested that the decrease in proliferation resulted from interactions between HIV-1 and the mouse cells, but did not involve IL-2/IL-2 receptor interactions. We used monoclonal antibodies to demonstrate that the HIV-1 envelope glycoproteins were required for the inhibition of murine T cell proliferation. Anti-gp120 antibodies completely restored proliferation, indicating that the surface protein gp120 was primarily required for the inhibition of proliferation. However, antibodies directed against the transmembrane protein of HIV-1 (gp41) also partially restored lymphocyte proliferation. The functional significance of the HIV-1 envelope protein epitopes recognized by the monoclonal antibodies is discussed.
由人类T细胞直接感染产生的HIV-1细胞病变效应并不能解释HIV感染过程中CD4阳性淋巴细胞不成比例的损失。先前的研究已经证明HIV-1包膜糖蛋白会抑制未感染的人类T细胞活化和增殖，推测这是由于gp120与CD4的相互作用所致。为了研究在不存在直接感染和gp120-CD4相互作用的情况下HIV-1抑制T细胞增殖的能力，我们测试了HIV-1对小鼠T细胞增殖的影响。含有从感染细胞释放的HIV-1的培养基抑制了T淋巴细胞对白细胞介素-2（IL-2）的增殖反应。探索这种抑制机制的研究表明，增殖的减少是由HIV-1与小鼠细胞之间的相互作用引起的，但不涉及IL-2/IL-2受体相互作用。我们使用单克隆抗体来证明HIV-1包膜糖蛋白是抑制小鼠T细胞增殖所必需的。抗gp120抗体完全恢复了增殖，表明表面蛋白gp120是抑制增殖的主要所需蛋白。然而，针对HIV-1跨膜蛋白（gp41）的抗体也部分恢复了淋巴细胞增殖。本文讨论了单克隆抗体所识别的HIV-1包膜蛋白表位的功能意义。
