Chan S H, Perussia B, Gupta J W, Kobayashi M, Pospísil M, Young H A, Wolf S F, Young D, Clark S C, Trinchieri G
Wistar Institute, Philadelphia, Pennsylvania 19104.
J Exp Med. 1991 Apr 1;173(4):869-79. doi: 10.1084/jem.173.4.869.
We previously reported that natural killer cell stimulatory factor (NKSF), a heterodimeric lymphokine purified from the conditioned medium of human B lymphoblastoid cell lines, induces interferon gamma (IFN-gamma) production from resting peripheral blood lymphocytes (PBL) and synergizes with interleukin 2 in this activity. In this study, we show that human NKSF induces IFN-gamma production from both resting and activated human PBL and from freshly isolated murine splenocytes. Human T and NK cells produce IFN-gamma in response to NKSF, but resting PBL require the presence of nonadherent human histocompatibility leukocyte antigens DR+ (HLA-DR+) accessory cells to respond to NKSF. The mechanism(s) by which NKSF induces IFN-gamma production results in accumulation of IFN-gamma mRNA, is insensitive to cyclosporin A, and synergizes with those mediated by phytohemagglutinin, phorbol diesters, anti-CD3 antibodies, and allogeneic antigens, but not by Ca2+ ionophores. The ability of NKSF to directly induce IFN-gamma production and to synergize with other physiological IFN-gamma inducers, joined with the previously described ability to enhance lymphocyte cytotoxicity and proliferation, indicates that this lymphokine is a powerful immunopotentiating agent.
我们先前报道过，自然杀伤细胞刺激因子（NKSF）是一种从人B淋巴母细胞系条件培养基中纯化得到的异二聚体淋巴因子，可诱导静息外周血淋巴细胞（PBL）产生γ干扰素（IFN-γ），并在此活性中与白细胞介素2协同作用。在本研究中，我们表明人NKSF可诱导静息和活化的人PBL以及新鲜分离的小鼠脾细胞产生IFN-γ。人T细胞和NK细胞对NKSF产生反应而分泌IFN-γ，但静息PBL需要存在非黏附性人组织相容性白细胞抗原DR+（HLA-DR+）辅助细胞才能对NKSF产生反应。NKSF诱导IFN-γ产生的机制会导致IFN-γ mRNA的积累，对环孢菌素A不敏感，并与植物血凝素、佛波酯、抗CD3抗体和同种异体抗原介导的机制协同作用，但不与Ca2+离子载体协同作用。NKSF直接诱导IFN-γ产生以及与其他生理性IFN-γ诱导剂协同作用的能力，再加上先前描述的增强淋巴细胞细胞毒性和增殖的能力，表明这种淋巴因子是一种强大的免疫增强剂。
