Liu M A, Liu T
Endocrine Unit, Massachusetts General Hospital, Boston.
J Clin Invest. 1988 Dec;82(6):2176-80. doi: 10.1172/JCI113842.
We have previously demonstrated that recombinant soluble CD4 protein (rsT4) blocks both HIV-1 infection of CD4 bearing lymphocytes and syncytium formation in vitro. (Recombinant soluble CD4 is designated by rsT4). Hence, we suggested the use of rsT4 in therapy for AIDS or the prevention of HIV-1 infection in individuals with a known risk of exposure. However, concerns arose that rsT4 might be immunosuppressive because of its implicated role in the enhancement of certain lymphocyte activation events through its engagement of MHC class II molecules on target cells. We therefore assessed the effect of recombinant soluble CD4 upon a number of functional and activation parameters of lymphocytes, including cellular proliferation, IL-2 secretion, and cytolytic capability, after antigenic or mitogenic stimulation. We report here that rsT4, at 60-fold over the concentration needed to block acute HIV-1 infection in vitro, does not significantly inhibit the activation of human peripheral blood lymphocytes by either PHA, tetanus toxoid or allogeneic cells. These results indicate that rsT4 will potentially exert minimal immunosuppressive effects in vivo, thus supporting the feasibility of clinical trials of rsT4 in the treatment or prevention of AIDS. In addition, the implications of these results for the interactions between CD4 and MHC class II molecules during lymphocyte activation are discussed.
我们先前已证明，重组可溶性CD4蛋白（rsT4）在体外可阻断HIV-1对表达CD4的淋巴细胞的感染以及合胞体的形成。（重组可溶性CD4用rsT4表示）。因此，我们建议将rsT4用于治疗艾滋病或预防已知有暴露风险个体的HIV-1感染。然而，有人担心rsT4可能具有免疫抑制作用，因为它通过与靶细胞上的MHC II类分子结合，在增强某些淋巴细胞激活事件中发挥作用。因此，我们评估了重组可溶性CD4对抗原或有丝分裂原刺激后淋巴细胞的一些功能和激活参数的影响，包括细胞增殖、IL-2分泌和细胞溶解能力。我们在此报告，rsT4的浓度比体外阻断急性HIV-1感染所需的浓度高60倍时，不会显著抑制PHA、破伤风类毒素或异基因细胞对人外周血淋巴细胞的激活。这些结果表明，rsT4在体内可能产生最小的免疫抑制作用，从而支持rsT4用于治疗或预防艾滋病的临床试验的可行性。此外，还讨论了这些结果对淋巴细胞激活过程中CD4与MHC II类分子之间相互作用的意义。
