Cell division regulates the T cell cytokine repertoire, revealing a mechanism underlying immune class regulation
Cell division regulates the T cell cytokine repertoire, revealing a mechanism underlying immune class regulation
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DOI：
10.1073/pnas.95.16.9488
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发表时间：
1998-08-04
影响因子：
11.1
通讯作者：
Hodgkin, PD
中科院分区：
文献类型：
--
作者：
Gett, AV;Hodgkin, PD
幼稚T淋巴细胞具有分化和产生一系列对适当免疫反应至关重要的细胞因子的潜力。T淋巴细胞在分化过程中如何改变其细胞因子输出尚不清楚，尽管它们明显受到环境中已经存在的细胞因子的影响。在这里，我们表明细胞在激活后的分裂次数是T细胞分化的关键因素。我们的实验使用染料5-（和6-）羧基荧光素二乙酸琥珀酰酰酯，在分化细胞因子白细胞介素(IL)-4存在的情况下，追踪抗cd3激活后不同分裂的细胞。白细胞介素-2、白细胞介素-3、白细胞介素-4、白细胞介素-5、白细胞介素-10和γ干扰素分泌的获得或丧失模式都随着分裂数的增加而显著变化。这些关系是一致的，不管T细胞分布在分裂中的时间依赖性变化。因此，观察到的复杂的异步T细胞生长的组合，覆盖了每次分裂时获得或失去细胞因子的固定概率，可以解释为什么T细胞分化显示出高度随机和高度控制的矛盾特征。此外，这些数据表明T细胞与B细胞具有共同的调节策略，即免疫反应类别的变化与克隆扩增过程有关。
Naive T lymphocytes have the potential to differentiate and produce a range of cytokines crucial for appropriate immune responses. Bow T lymphocytes vary their cytokine output during differentiation is unknown, although they are clearly influenced by the cytokines already present in the environment. Here we show that the number of divisions taken by the cells after activation is a critical element in T cell differentiation. Our experiments used the dye 5- (and 6-) carboxyfluorescein diacetate, succinimidyl ester to track cells in different divisions after activation by anti-CD3 in the presence of the differentiating cytokine interleukin (IL)-4. The patterns of acquisition or loss of secretion of IL-2, IL-3, IL-4, IL-5, IL-10, and interferon gamma all varied markedly with division number. These relationships were consistent regardless of the time-dependent variation in distribution of T cells among divisions. Thus, the observed combination of complex asynchronous T cell growth, overlaying a fixed probability of acquisition or loss of a cytokine at each division can explain why T cell differentiation displays the contradictory features of being both highly stochastic and highly controlled. Furthermore, these data reveal that T cells share a common regulatory strategy with B cells, whereby changes in the class of immune response are linked to the process of clonal expansion.