The molecular program induced in T cells undergoing homeostatic proliferation
The molecular program induced in T cells undergoing homeostatic proliferation
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DOI：
10.1073/pnas.0407417101
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发表时间：
2004-11-30
影响因子：
11.1
通讯作者：
Mathis, D
中科院分区：
文献类型：
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作者：
Goldrath, AW;Luckey, CJ;Mathis, D
当引入淋巴细胞减少的宿主时，幼稚T细胞独立于同源抗原增殖。淋巴细胞减少的增殖依赖于低亲和力MHC/自肽复合物和IL-7。为了阐明介导这种增殖的细胞内信号，我们分析了初始CD8(+) T细胞在转移到淋巴细胞减少环境后不同时间基因表达的变化。在淋巴细胞减少反应中诱导的基因主要是在完全抗原刺激下出现的基因的弱化子集，包括与细胞循环相关的基因，而不包括与效应活性特异性相关的基因。在空腔室中增殖初始阶段后，幼稚T细胞采用了与抗原经历记忆细胞相似的稳定的基因表达模式。因此，在淋巴细胞减少的宿主中增殖的T细胞不表现出独特的基因表达谱，而是依靠“传统”信号进行这种抗原无关的增殖；这个过程最终导致分化为“真正的”记忆细胞。
Naive T cells proliferate independently of cognate antigen when introduced into lymphopenic hosts. Lymphopenia-incluced proliferation depends on low-affinity MHC/self-peptide complexes and on IL-7. To elucidate the intracellular signals mediating this proliferation, we analyzed changes in gene expression in naive CD8(+) T cells at different times after their transfer into a lymphopenic environment. The genes induced in response to lymphopenia were largely an attenuated subset of those turned up by full antigenic stimulation, including genes related to cell cycling, whereas excluding genes specifically associated with effector activity. After the initial phase of proliferation in an empty compartment, the naive T cells adopted a stable pattern of gene expression similar to that of antigen-experienced memory cells. Thus, T cells proliferating in lymphopenic hosts do not exhibit a unique gene-expression profile, instead relying on "traditional" signals for this antigenindependent proliferation; this process ultimately results in differentiation to "authentic" memory cells.