中文摘要：

目的：观察VIR576对CD4＋T细胞活化的作用。方法分离DO11.10小鼠脾细胞并用OVA或ConA分别刺激，观察VIR576对抗原特异性和非特异性T细胞活化的影响；培养A2b CD4＋T细胞株和磁珠分离的DO11.10小鼠脾脏CD4＋CD25-效应性T细胞，分别用特异性抗原激活，观察VIR576对抗原特性CD4＋T细胞活化的影响。结果 VIR576抑制抗原特异性T细胞的活化，但对非抗原特异性T细胞活化的影响不显著，非特异性T细胞活化不需要TCR和CD3的交联。进一步研究发现，VIR576也可以下调抗原特异性CD4＋T细胞的活化。结论粘膜活化的CD4＋T细胞对HIV-1高度易感，VIR576不仅具有抑制HIV进入的活性还能够抑制CD4＋T细胞活化，提示VIR576是一种有开发潜能的预防HIV性传播的杀微生物剂。

英文摘要：

Objective To observe if VIR576, an 20-mer peptide derived from the C-proximal subfragment of a1-antitrypsin （a1-AT） which inhibits human immunodeficiency virus type 1 （HIV-1） entry into the target cells by interacting with fusion peptide （FP）, can also directly inhibit CD4＋T cell activation in vitro. Methods Splenocytes isolated from DO11.10 OVA Tg mice were stimulated with ovalbumin or concanavalin A to test the effects of VIR576 on antigen-specific or non-antigen-specific T cell activation. Both primary CD4＋CD25-T cells from DO11.10 mice and CD4＋T cell line A2b were activated with specific antigens to evaluate the effects of VIR576. Results VIR576 inhibited antigen-specific splenocyte activation but had no significant effect on non-antigen-specific T-cell activation, which bypassed the crosstalk between the CD3-signaling complex and TCR. We furthermore observed that VIR576 could also down-regulate antigen-specific CD4＋ T-cell activation. Conclusion Given the high susceptibility of activated CD4＋ T cells in the mucosa to HIV-1 infection, the inhibitory effects of VIR576 on both HIV entry into the target cells and CD4＋T-cell activation suggest the potential of VIR576 as a microbicide for prevention of sexual transmission of HIV.