Ramarathinam L, Niesel D W, Klimpel G R
Department of Microbiology, University of Texas Medical Branch, Galveston 77555-1019.
J Immunol. 1993 May 1;150(9):3973-81.
IFN-gamma is a cytokine known to play an important role in host defense against Salmonella typhimurium. The lymphoid cells required for in vitro production of IFN-gamma after S. typhimurium stimulation of mouse spleen cells was investigated. Spleen cells depleted of cells bearing NK1.1, asialo GM1, Thy 1.2, or CD5 resulted in a significant reduction in IFN-gamma production after stimulation with S. typhimurium. In contrast, Con A-induced IFN-gamma production was only slightly reduced after depletion of NK1.1- or asialo GM1-bearing cells. Spleen cells from SCID mice produced elevated levels of IFN-gamma after stimulation with S. typhimurium. IFN-gamma production by SCID spleen cells was dependent upon asialo GM1+ T cells, suggesting that NK cells were the cells producing IFN-gamma in response to S. typhimurium. Splenic adherent cells were required for optimal IFN-gamma production. However, direct contact between the adherent and nylon wool nonadherent (NWNA) cell populations was not essential. IFN-gamma production was observed when the adherent and NWNA cell populations were physically separated or when supernatant from S. typhimurium-stimulated adherent cells was added to NWNA cells. Optimal IFN-gamma production was dependent on the presence of TNF-alpha, inasmuch as addition of antibody to TNF-alpha to spleen cell or NWNA cell cultures significantly reduced IFN-gamma production. However, addition of rTNF-alpha did not induce IFN-gamma production by NWNA cells. These findings document the existence of a T-independent mechanism for early IFN-gamma production in response to S. typhimurium, and show that TNF-alpha is necessary but not sufficient for the production of IFN-gamma.
干扰素-γ是一种细胞因子，已知在宿主抵御鼠伤寒沙门氏菌的防御中发挥重要作用。研究了鼠伤寒沙门氏菌刺激小鼠脾细胞后体外产生干扰素-γ所需的淋巴细胞。去除携带NK1.1、脱唾液酸GM1、Thy 1.2或CD5的细胞后，鼠伤寒沙门氏菌刺激后干扰素-γ的产生显著减少。相比之下，去除携带NK1.1或脱唾液酸GM1的细胞后，Con A诱导的干扰素-γ产生仅略有减少。SCID小鼠的脾细胞在受到鼠伤寒沙门氏菌刺激后产生的干扰素-γ水平升高。SCID脾细胞产生干扰素-γ依赖于脱唾液酸GM1+T细胞，这表明NK细胞是响应鼠伤寒沙门氏菌产生干扰素-γ的细胞。脾黏附细胞是干扰素-γ最佳产生所必需的。然而，黏附细胞和尼龙毛非黏附（NWNA）细胞群体之间的直接接触并非必需。当黏附细胞和NWNA细胞群体物理分离时，或者当鼠伤寒沙门氏菌刺激的黏附细胞的上清液添加到NWNA细胞中时，观察到干扰素-γ的产生。干扰素-γ的最佳产生依赖于TNF-α的存在，因为向脾细胞或NWNA细胞培养物中添加抗TNF-α抗体显著降低了干扰素-γ的产生。然而，添加rTNF-α并未诱导NWNA细胞产生干扰素-γ。这些发现证明了存在一种不依赖T细胞的机制来早期响应鼠伤寒沙门氏菌产生干扰素-γ，并表明TNF-α对于干扰素-γ的产生是必要的但不是充分的。
