Blanchard D K, Djeu J Y, Klein T W, Friedman H, Stewart W E
J Immunol. 1986 Feb 1;136(3):963-70.
Bacterial lipopolysaccharide (LPS) induced fresh murine splenocytes to produce interferon (IFN)-alpha/beta presumably by stimulation of the B lymphocytes and macrophages. However, when the splenocytes were "aged" for 24 to 72 hr in culture before addition of the LPS, the IFN response was significantly increased and was determined to be predominantly IFN-gamma. Because low levels of interleukin 2 (IL 2) were found to be spontaneously produced by the unstimulated splenocytes during the "aging" process, the effect of IL 2 on IFN induction by LPS in fresh splenocytes was examined. The addition of LPS to freshly prepared splenocyte cultures that were treated with human IL 2, either native or recombinant, before exposure to the LPS resulted in the LPS inducing large amounts of IFN-gamma. IL 2 alone induced little if any IFN in the splenocyte cultures. Depletion of T cells and large granular lymphocytes (LGL) from the cultures by anti-Thy-1.2 antibodies plus complement abrogated IFN-gamma production, and the addition of polymyxin B to "aged" splenocyte cultures resulted in loss of IFN production in response to LPS. Cultures that were enriched for T cells and LGL by passage through nylon wool produced significant amounts of IFN-gamma in response to LPS only if first treated with IL 2. Furthermore, the addition of splenic adherent cells to purified nylon wool-non-adherent (NWNA) cells augmented IFN-gamma production, whether or not the NWNA cells were pretreated with IL 2. This enhancement appeared to require direct contact between adherent cells and NWNA cells, because physical separation abrogated IFN production. The addition of recombinant IL 1 or LPS-conditioned supernatants of macrophage cultures did not replace adherent cell activity. These data demonstrate that LPS, which predominantly induces IFN-alpha/beta in fresh murine splenocytes, is able to stimulate T lymphocytes to produce IFN-gamma if the T cells are first exposed to endogenously produced or exogenously applied IL 2. Because IFN-gamma is a potent activator of the bactericidal and cytocidal potential of macrophages, the induction of IFN-gamma by bacterial LPS may play an important role in resistance/recovery mechanisms against bacterial infections.
细菌脂多糖(LPS)可能通过刺激B淋巴细胞和巨噬细胞,诱导新鲜的小鼠脾细胞产生α/β干扰素(IFN)。然而,在添加LPS之前,若将脾细胞在培养中“老化”24至72小时,IFN反应会显著增强,且确定主要为γ干扰素。由于在“老化”过程中发现未受刺激的脾细胞会自发产生低水平的白细胞介素2(IL-2),因此研究了IL-2对新鲜脾细胞中LPS诱导IFN的影响。在暴露于LPS之前,向用天然或重组人IL-2处理过的新鲜制备的脾细胞培养物中添加LPS,会导致LPS诱导大量γ干扰素。单独的IL-2在脾细胞培养物中几乎不诱导IFN。用抗Thy-1.2抗体加补体从培养物中去除T细胞和大颗粒淋巴细胞(LGL)可消除γ干扰素的产生,向“老化”的脾细胞培养物中添加多粘菌素B会导致对LPS的IFN产生丧失。通过尼龙棉柱富集T细胞和LGL的培养物,只有在先用IL-2处理后,才会对LPS产生大量γ干扰素。此外,无论尼龙棉非贴壁(NWNA)细胞是否先用IL-2预处理,向纯化的NWNA细胞中添加脾贴壁细胞都会增强γ干扰素的产生。这种增强似乎需要贴壁细胞与NWNA细胞直接接触,因为物理分离会消除IFN的产生。添加重组IL-1或巨噬细胞培养物的LPS条件上清液并不能替代贴壁细胞的活性。这些数据表明,在新鲜小鼠脾细胞中主要诱导α/β干扰素的LPS,如果T细胞首先暴露于内源性产生或外源性应用的IL-2,就能够刺激T淋巴细胞产生γ干扰素。由于γ干扰素是巨噬细胞杀菌和杀细胞潜能的有效激活剂,细菌LPS诱导γ干扰素可能在抵抗/抵御细菌感染的机制中起重要作用。