Induction of immunoglobulin synthesis by CD4+ T cell clones.

Induction of immunoglobulin synthesis by CD4+ T cell clones.
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DOI:
10.1006/smim.1993.1048
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发表时间:
1993-12-01
影响因子:
7.8
通讯作者:
Umetsu, D T
Umetsu, D T
中科院分区:
医学2区
文献类型:
--
作者:
DeKruyff, R H;Rizzo, L V;Umetsu, D T

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由于获得了具有有限细胞因子谱的CD 4 + T细胞克隆,CD 4 + T细胞诱导IG合成的机制研究得到了极大的加强。我们已经通过体外和体内研究证明,Th 1(T辅助细胞1)和Th 2克隆都可以提供MHC限制性帮助,并在同源抗原驱动条件下诱导初级和二级抗体应答。此外,我们已经表明,这两种类型的克隆,利用不同的细胞因子,可以影响B细胞的记忆和亲和力成熟的IG的反应,虽然这发生的确切机制尚不清楚。使用Th 1和Th 2克隆,我们还表明IgG 1合成的途径是多余的,因为在B细胞已经从IgM转换为IgG 1的次级应答中,IgG 1合成的诱导可以通过几种途径发生,一种涉及IL-4和IL-5,另一种涉及IL-2。相反,IgE和IgG 2a的合成需要特异性细胞因子用于在原代和次级B细胞中的合成。最后,当两种类型的克隆都存在于初级IG应答的诱导过程中时,由Th 1和Th 2克隆产生的细胞因子可以相互“中和”。然而,作为例外,伊加合成的诱导被两种类型的克隆的存在大大增强。
The study of mechanisms by which CD4+ T cells induce Ig synthesis has been greatly enhanced by the availability of CD4+ T cell clones with restricted cytokine profiles. We have demonstrated with in vitro and in vivo studies that both Th1 (T helper cell 1) and Th2 clones can provide MHC restricted help and induce primary as well as secondary antibody responses under cognate antigen driven conditions. In addition, we have shown that both types of clones, utilizing distinct cytokines, can effect B cell memory and affinity maturation of the Ig response, although the precise mechanisms by which this occurs are not yet clear. Using Th1 and Th2 clones, we have also shown that the pathways for IgG1 synthesis are redundant, in that induction of IgG1 synthesis in secondary responses in which B cells have already switched from IgM to IgG1, can occur via several pathways, one involving IL-4 and IL-5, the other involving IL-2. In contrast, IgE and IgG2a synthesis require specific cytokines for synthesis in both primary and secondary B cells. Finally, the cytokines produced by Th1 and Th2 clones can 'neutralize' each other, when both types of clones are present during the induction of primary Ig responses. As an exception however, the induction of IgA synthesis is greatly augmented by the presence of both types of clones.