Schweitzer A N, Anderson R M
Wellcome Research Centre for Parasitic Diseases, Biology Department, Imperial College, London University, U.K.
Proc Biol Sci. 1992 Feb 22;247(1319):107-12. doi: 10.1098/rspb.1992.0015.
It is well established that specific unresponsiveness to immunization can be induced by prolonged exposure to antigenic proteins. More generally, many parasitic infections, such as the helminth worms and the Leishmania parasites, appear to be able to persist in some of their human hosts over long periods of time, via what appears to be an ability to induce defective or inappropriate T-cell responses (= tolerance). Recent research has suggested that cytokines, produced by specific subsets of CD4+ T-cells (characterized by cytokine secretory profiles and growth properties), have an important, and often complex, role in promoting or inhibiting host protective immunity to parasitic infections. By examination of the population dynamics of the stimulation and regulation of cellular responses to infection, via the use of simple mathematical models, we show that nonlinear interactions between CD4+ T-cell subsets and their secreted cytokines can result in either host protection or immunological unresponsiveness, depending on the magnitude and duration of exposure to parasitic infection. Analyses also identify a possible mechanism to explain the stimulation of two separate peaks of enhanced T-cell-mediated responses over a wide range of levels of antigenic exposure.
长期暴露于抗原性蛋白质可诱导对免疫接种的特异性无反应性，这一点已得到充分证实。更普遍地说，许多寄生虫感染，如蠕虫和利什曼原虫寄生虫，似乎能够通过诱导有缺陷或不适当的T细胞反应（即耐受性），在其一些人类宿主中长期存在。最近的研究表明，由特定CD4 + T细胞亚群产生的细胞因子（以细胞因子分泌谱和生长特性为特征）在促进或抑制宿主对寄生虫感染的保护性免疫中具有重要且通常复杂的作用。通过使用简单的数学模型检查对感染的细胞反应的刺激和调节的群体动态，我们表明CD4 + T细胞亚群与其分泌的细胞因子之间的非线性相互作用可导致宿主保护或免疫无反应性，这取决于暴露于寄生虫感染的程度和持续时间。分析还确定了一种可能的机制，以解释在广泛的抗原暴露水平上增强的T细胞介导反应的两个独立峰值的刺激。
