On the mechanism determining the TH1/TH2 phenotype of an immune response, and its pertinence to strategies for the prevention, and treatment, of certain infectious diseases.
On the mechanism determining the TH1/TH2 phenotype of an immune response, and its pertinence to strategies for the prevention, and treatment, of certain infectious diseases.
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DOI：
10.1111/sji.12175
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发表时间：
2014-06
影响因子：
3.7
通讯作者：
Bretscher PA
中科院分区：
文献类型：
--
作者：
Bretscher PA
众所周知，针对外来或自身抗原的免疫反应的生理/病理后果往往严重依赖于所产生的免疫类别。在这里，我们重点研究抗原如何与免疫系统的细胞相互作用，以确定抗原主要是产生Th1细胞还是Th2细胞。我们将这一机制称为控制免疫反应的Th1/Th2表型的‘决定标准’。一个合理的决策标准应该考虑免疫变量，这些变量已知会影响随后免疫反应的Th1/Th2表型。记录在案的变量包括抗原的性质，就其外来程度而言，抗原的剂量和免疫后评估免疫反应的Th1/Th2表型的时间。这些都是在系统层面上做出的量化变量。此外，免疫接种的途径也很关键。我描述了一个关于决策标准性质的定量假设，称为阈值假设。这一假设解释了免疫的数量变量，这些变量会影响产生的免疫反应的Th1/Th2表型。我建议并举例说明，对于相互竞争的当代假说，这并不是真的。我概述了测试这一假设预测的研究，并说明了它在设计策略以预防或治疗医疗情况方面的潜在效用，在这些情况下，需要主要的Th1反应来遏制感染，例如由艾滋病毒-1和结核分枝杆菌引起的感染，或遏制癌症。
It is well recognized that the physiological/pathological consequences of an immune response, against a foreign or a self-antigen, are often critically dependent on the class of immunity generated. Here we focus on how antigen interacts with the cells of the immune system to determine whether antigen predominantly generates Th1 or Th2 cells. We refer to this mechanism as the ‘decision criterion’ controlling the Th1/Th2 phenotype of the immune response. A plausible decision criterion should account for the variables of immunization known to affect the Th1/Th2 phenotype of the ensuing immune response. Documented variables include the nature of the antigen, in terms of its degree of foreignness, the dose of antigen and the time after immunization at which the Th1/Th2 phenotype of the immune response is assessed. These are quantitative variables made at the level of the system. In addition, the route of immunization is also critical. I describe a quantitative hypothesis as to the nature of the decision criterion, referred to as the Threshold Hypothesis. This hypothesis accounts for the quantitative variables of immunization known to affect the Th1/Th2 phenotype of the immune response generated. I suggest and illustrate how this is not true of competing, contemporary hypotheses. I outline studies testing predictions of the hypothesis and illustrate its potential utility in designing strategies to prevent or treat medical situations where a predominant Th1 response is required to contain an infection, such as those caused by HIV-1 and by Mycobacterium tuberculosis, or to contain cancers.
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DOI：
10.1084/jem.182.5.1591
发表时间：
1995-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Constant S;Pfeiffer C;Woodard A;Pasqualini T;Bottomly K
通讯作者：
Bottomly K
影响因子：
15.3
作者：
Karlsson, MR;Rugtveit, J;Brandtzaeg, P
通讯作者：
Brandtzaeg, P
DOI：
10.1084/jem.169.1.59
发表时间：
1989-01-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Heinzel FP;Sadick MD;Holaday BJ;Coffman RL;Locksley RM
通讯作者：
Locksley RM
影响因子：
3.7
作者：
Abdi, K.;Singh, N.;Matzinger, P.
通讯作者：
Matzinger, P.
影响因子：
56.9
作者：
Fearon, DT;Locksley, RM
通讯作者：
Locksley, RM