Alloantibody production is regulated by CD4+ T cells' alloreactive pathway, rather than precursor frequency or Th1/Th2 differentiation
Alloantibody production is regulated by CD4+ T cells' alloreactive pathway, rather than precursor frequency or Th1/Th2 differentiation
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DOI：
10.1111/j.1600-6143.2004.00520.x
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发表时间：
2004-08-01
影响因子：
8.8
通讯作者：
Daniel, C
中科院分区：
文献类型：
--
作者：
Sauvé, D;Baratin, M;Daniel, C
虽然CD 4（+）T细胞在同种异体移植排斥反应的调节中起重要作用，但它们的确切作用机制以及直接和间接同种异体反应性途径的实际作用仍有待充分表征。以前的研究已经建立了间接同种异体反应性途径和抗体产生之间的可能关系，但这些研究中使用的模型固有的缺点使这些结果的解释变得复杂。为了解决这个问题，我们已经开发了一种基于TCR转基因小鼠的模型，该小鼠来源于CD 4（+）T细胞克隆，其通过两种同种异体反应性途径识别特异性同种异体抗原。将转基因CD 4（+）T细胞过继转移到α-T细胞缺陷小鼠的皮肤同种异体移植物在两种同种异体反应性途径之间没有明显延迟。单独通过直接同种异体反应性途径在同种异体移植排斥反应后不产生IgG同种抗体。重要的是，针对直接途径的同种异体抗原的抗体的产生被证明需要间接途径激活的CD 4（+）T细胞的帮助。这些结果表明，导致移植物排斥反应的免疫应答的启动的事件显然依赖于参与T淋巴细胞和B淋巴细胞活化的抗原呈递细胞的群体。
Although CD4(+) T cells play an important role in the regulation of allograft rejection, the exact mechanisms by which they operate and the actual contribution of direct and indirect alloreactivity pathways remain to be fully characterized. Previous studies have established a possible relationship between the indirect alloreactivity pathway and antibody production, but interpretation of these results have been complicated by shortcomings inherent to the models used in these studies. To address this issue, we have developed a model based on TCR transgenic mice derived from a CD4(+) T-cell clone which recognize specific alloantigens by both alloreactivity pathways. Skin allografts on alphabeta T-cell deficient mice adoptively transferred with transgenic CD4(+) T cells were rejected without significant delay between the two alloreactivity pathways. No IgG alloantibody was produced following allograft rejection by the direct alloreactivity pathway alone. Importantly, production of antibodies against alloantigens of the direct pathway was shown to require help from CD4(+) T cells activated by the indirect pathway. These results indicate that the events leading to the initiation of immune responses responsible for graft rejection are clearly dependent on the population of antigen-presenting cells involved in T- and B-lymphocyte activation.