Rizzo L V, DeKruyff R H, Umetsu D T, Caspi R R
National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1858, USA.
Eur J Immunol. 1995 Mar;25(3):708-16. doi: 10.1002/eji.1830250312.
On the premise that an individual with an intact immune system has the capability to develop both cellular and antibody immune responses supported by the balance between the lymphokines secreted by T helper (Th) cells, we studied the interaction between different types of Th cell clones in vivo and the parameters that may affect this interaction. We used an adoptive transfer system in which nude or lethally irradiated mice were reconstituted with histocompatible CD4+ keyhole limpet hemocyanin (KLH)-specific T cell clones with defined lymphokine profiles. This approach allowed us to study the effects of the cognate interaction between T and B cells in the presence of a defined set of lymphokines. We demonstrated that the co-transfer of both subsets of Th cells resulted in increased production of IgA, and decreased production of IgE and IgG2a. The concomitant presence of both cell types also increases their functional survival in vivo. We have shown that in the presence of a Th2 clone, higher immunization doses (above 100 micrograms trinitrophenol (TNP)-KLH/mouse) result in increased production of IgE and IgG1. In contrast, when a Th1 clone is present, low immunization doses (less than 50 micrograms TNP-KLH/mouse) resulted in increased production of IgG2a. We were also able to show that the neutralization of interleukin-4(IL-4) and or interferon-gamma (IFN-gamma) was sufficient to abrogate most of the regulatory effects caused by the Th2 or the Th1 clone respectively. Our results indicate that the subset of T cell(s) transferred determines the type of response obtained. In addition, the data presented indicate that the antigen dose used for immunization can modulate the quantitative parameters of the response. Furthermore, we have shown that the interaction between the two subsets of T cells in vivo is characterized by both antagonistic and agonistic effects and that most of the regulatory effects exerted by one subset over the other are mediated by IL-4 or IFN-gamma.
在具有完整免疫系统的个体有能力产生由辅助性T（Th）细胞分泌的淋巴因子之间的平衡所支持的细胞免疫和抗体免疫反应这一前提下，我们研究了不同类型的Th细胞克隆在体内的相互作用以及可能影响这种相互作用的参数。我们使用了一种过继转移系统，其中裸鼠或经致死性照射的小鼠用具有确定淋巴因子谱的组织相容性CD4 + 钥孔戚血蓝蛋白（KLH）特异性T细胞克隆进行重建。这种方法使我们能够在一组确定的淋巴因子存在的情况下研究T细胞和B细胞之间同源相互作用的影响。我们证明，两种Th细胞亚群的共同转移导致IgA产生增加，IgE和IgG2a产生减少。两种细胞类型的同时存在也增加了它们在体内的功能存活。我们已经表明，在存在Th2克隆的情况下，较高的免疫剂量（超过100微克三硝基苯酚（TNP）-KLH/小鼠）导致IgE和IgG1产生增加。相反，当存在Th1克隆时，低免疫剂量（小于50微克TNP-KLH/小鼠）导致IgG2a产生增加。我们还能够表明，白细胞介素-4（IL-4）和/或干扰素-γ（IFN-γ）的中和分别足以消除由Th2或Th1克隆引起的大部分调节作用。我们的结果表明，转移的T细胞亚群决定了所获得的反应类型。此外，所呈现的数据表明用于免疫的抗原剂量可以调节反应的定量参数。此外，我们已经表明，体内两种T细胞亚群之间的相互作用具有拮抗和激动作用的特征，并且一个亚群对另一个亚群施加的大部分调节作用是由IL-4或IFN-γ介导的。
