Nair M P, Schwartz S A
Department of Medicine, State University of New York at Buffalo, Buffalo General Hospital 14203, USA.
Cell Mol Biol (Noisy-le-grand). 1997 Nov;43(7):969-79.
Recombinant and synthetic peptides derived from the human immunodeficiency virus type I (HIV-1) genome corresponding to portions of the envelope (env) and internal core protein (gag) were examined for their immunoregulatory effects on the natural killer (NK) cell activity of lymphocytes from healthy donors and from patients with the acquired immunodeficiency syndrome (AIDS). Two recombinant peptides (env-gag and Env 80-DHFR) and three chemically synthesized peptides (env 487-511, env 578-608 and env 647-659) were used. Normal lymphocytes precultured for 24 to 72 hrs. with either env-gag, env 487-511, or env 647-659 at 5 and 50 ng/ml concentrations which significantly stimulated lymphocyte proliferation, produced significant suppression of NK activities. Two control peptides, one derived from the E. coli vector used to clone the HIV env-gag fusion peptide and another, a non-HIV-1 viral antigen (rubeola virus) did not produce any observable effect on NK activity of normal lymphocytes demonstrating the specificity of the reaction. Env-gag peptide also inhibited the NK activities of Percoll-separated, NK-enriched large granular lymphocytes. In target binding assays, lymphocytes precultured with env-gag significantly suppressed the target binding capacity of effector cells and produced significantly lower levels of natural killer cytotoxic factor (NKCF). In kinetic studies, lymphocytes from normal donors preincubated with env-gag for 24 to 72 hrs. produced significant inhibition of their NK activity and an even greater inhibitory effect on NK activities was observed when lymphocytes from AIDS patients were preincubated with HIV peptides. Thus HIV-1 peptides, which we previously demonstrated could regulate B- and T-lymphocyte activities, are also capable of regulating the NK activities of lymphocytes from HIV-1-infected and normal individuals.
对源自人类免疫缺陷病毒I型（HIV-1）基因组、对应包膜（env）和内部核心蛋白（gag）部分的重组肽和合成肽，检测了它们对健康供体及获得性免疫缺陷综合征（AIDS）患者淋巴细胞自然杀伤（NK）细胞活性的免疫调节作用。使用了两种重组肽（env-gag和Env 80-DHFR）以及三种化学合成肽（env 487-511、env 578-608和env 647-659）。正常淋巴细胞在5和50 ng/ml浓度的env-gag、env 487-511或env 647-659中预培养24至72小时，这些浓度可显著刺激淋巴细胞增殖，同时产生显著的NK活性抑制。两种对照肽，一种源自用于克隆HIV env-gag融合肽的大肠杆菌载体，另一种是非HIV-1病毒抗原（风疹病毒），对正常淋巴细胞的NK活性未产生任何可观察到的影响，证明了反应的特异性。Env-gag肽也抑制了经Percoll分离的、富含NK的大颗粒淋巴细胞的NK活性。在靶细胞结合试验中，用env-gag预培养的淋巴细胞显著抑制了效应细胞的靶细胞结合能力，并产生了显著更低水平的自然杀伤细胞毒性因子（NKCF）。在动力学研究中，正常供体的淋巴细胞与env-gag预孵育24至72小时，其NK活性产生显著抑制，当AIDS患者的淋巴细胞与HIV肽预孵育时，观察到对NK活性有更大的抑制作用。因此，我们先前证明能够调节B淋巴细胞和T淋巴细胞活性的HIV-1肽，也能够调节来自HIV-1感染个体和正常个体淋巴细胞的NK活性。
