Hunter C A, Ellis-Neyer L, Gabriel K E, Kennedy M K, Grabstein K H, Linsley P S, Remington J S
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104, USA.
J Immunol. 1997 Mar 1;158(5):2285-93.
We examined the role of the CD28/B7 interaction in regulation of NK cell activity. Cells transfected with B7 enhanced IL-12-induced production of IFN-gamma by IL-2-activated, CD28+ NK cells, but not by resting CD28- NK cells. The ability of B7 transfectants to enhance NK cell production of IFN-gamma was dependent on the intracellular adhesion molecule-1/LFA-1 interaction and could be inhibited by TGF-beta, but not IL-10. Since IL-12-induced production of IFN-gamma by NK cells is associated with resistance to certain infections, we examined whether the CD28/B7 interaction regulated NK cell responses during infection. Infection of SCID mice with Toxoplasma gondii resulted in the appearance of a population of CD28+ NK cells, NK cell production of IFN-gamma, and increased NK cell cytolytic activity. Administration of CTLA4-Ig to SCID mice infected with T. gondii inhibited these latter two effects and resulted in a significant increase in parasite burden. The stimulus for CD28 expression by NK cells in SCID mice infected with T. gondii appeared to be independent of IL-2. However, mRNA for IL-15, a cytokine with properties similar to those of IL-2, was detected in tissues of SCID mice infected with T. gondii. In vitro experiments demonstrated that IL-15 could stimulate resting NK cells to express functionally active CD28 as well as enhance the production of IFN-gamma by SCID splenocytes stimulated with T. gondii. Together our data demonstrate that the interaction of CD28+ NK cells with B7 regulates NK cell production of IFN-gamma associated with resistance to infection and that IL-15 may be involved in these events.
我们研究了CD28/B7相互作用在调节自然杀伤（NK）细胞活性中的作用。用B7转染的细胞增强了IL-12诱导的、由IL-2激活的CD28+NK细胞产生γ干扰素的能力，但对静息的CD28-NK细胞无此作用。B7转染细胞增强NK细胞产生γ干扰素的能力依赖于细胞间黏附分子-1/LFA-1相互作用，且可被转化生长因子-β（TGF-β）抑制，但不受白细胞介素-10（IL-10）抑制。由于NK细胞IL-12诱导产生γ干扰素与对某些感染的抵抗力相关，我们研究了CD28/B7相互作用在感染期间是否调节NK细胞反应。用刚地弓形虫感染重症联合免疫缺陷（SCID）小鼠导致出现一群CD28+NK细胞、NK细胞产生γ干扰素以及NK细胞溶细胞活性增加。给感染刚地弓形虫的SCID小鼠注射CTLA4-Ig可抑制后两种效应，并导致寄生虫负荷显著增加。感染刚地弓形虫的SCID小鼠中NK细胞CD28表达的刺激似乎独立于IL-2。然而，在感染刚地弓形虫的SCID小鼠组织中检测到白细胞介素-15（IL-15）的信使核糖核酸（mRNA），IL-15是一种与IL-2性质相似的细胞因子。体外实验表明，IL-15可刺激静息NK细胞表达功能活跃的CD28，并增强受刚地弓形虫刺激的SCID脾细胞产生γ干扰素的能力。我们的数据共同表明，CD28+NK细胞与B7的相互作用调节与抗感染相关的NK细胞产生γ干扰素，且IL-15可能参与这些事件。
