Li S P, Lee S I, Domer J E
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Infect Immun. 1998 Apr;66(4):1392-9. doi: 10.1128/IAI.66.4.1392-1399.1998.
We have shown previously that intravenous injection of Candida albicans mannan (MAN) into naive mice induced CD8+ effector downregulatory cells and that such cells were not produced if mice were deficient in CD4+ or I-A+ cells during the early interval (< or =30 h) following the introduction of MAN. Moreover, the nonspecific biological response modifier monophosphoryl lipid A (MPL), given in vivo or incubated with cells in vitro, can abrogate the MAN-specific immunomodulatory activity. The mechanism by which the abrogation is mediated is unknown, but it is hypothesized to involve cytokines. Therefore, we measured the number of cytokine-secreting cells for the Thl cytokine interleukin-2 (IL-2) and the Th2 cytokine IL-4, as well as for gamma interferon (IFN-gamma), in splenocyte populations from MAN and/or MPL-treated mice, using an enzyme-linked immunospot assay designed to detect individual cytokine-secreting cells (spot-forming cells [SFC]). Cytokine-secreting cells were demonstrated in cell suspensions enriched for CD4+ cells, but no SFC could be demonstrated in populations enriched for CD8+ cells. Both MAN and MPL, when administered to separate groups of animals, stimulated the production of increased numbers of cytokine-producing cells for each of the three cytokines tested. The response with respect to IL-4-secreting cells, however, was the most striking. Despite the fact that MAN and MPL independently caused increases in SFC to all three cytokines, when both MAN and MPL were administered to the same animal, all increases were reversed, and the numbers of SFC detected were at or below those detected in saline control animals. These data support the hypothesis that IL-4 is involved in MAN-specific immunoregulatory activities. The data also emphasize the fact that two immunomodulators, i.e., MAN and MPL, having similar effects when given in vivo independently, may be antagonistic when administered sequentially to the same animal.
我们之前已经表明，向未接触过抗原的小鼠静脉注射白色念珠菌甘露聚糖（MAN）可诱导CD8 +效应下调细胞，并且如果在引入MAN后的早期间隔（≤30小时）内小鼠缺乏CD4 +或I - A +细胞，则不会产生此类细胞。此外，体内给予或体外与细胞孵育的非特异性生物反应调节剂单磷酰脂质A（MPL）可消除MAN特异性免疫调节活性。消除作用的介导机制尚不清楚，但据推测涉及细胞因子。因此，我们使用旨在检测单个细胞因子分泌细胞（斑点形成细胞[SFC]）的酶联免疫斑点试验，测量了来自MAN和/或MPL处理小鼠的脾细胞群体中Th1细胞因子白细胞介素-2（IL-2）、Th2细胞因子IL-4以及γ干扰素（IFN-γ）的细胞因子分泌细胞数量。在富含CD4 +细胞的细胞悬液中证实了细胞因子分泌细胞，但在富含CD8 +细胞的群体中未证实有SFC。当分别给予不同组动物时，MAN和MPL均刺激了所测试的三种细胞因子中每种细胞因子产生细胞数量的增加。然而，关于IL-4分泌细胞的反应最为显著。尽管MAN和MPL独立导致所有三种细胞因子的SFC增加，但当将MAN和MPL都给予同一只动物时，所有增加都被逆转，并且检测到的SFC数量等于或低于在生理盐水对照动物中检测到的数量。这些数据支持IL-4参与MAN特异性免疫调节活性的假设。数据还强调了这样一个事实，即两种免疫调节剂，即MAN和MPL，在体内单独给予时具有相似的效果，但当依次给予同一只动物时可能具有拮抗作用。
