Goldrath Ananda W, Luckey C John, Park Richard, Benoist Christophe, Mathis Diane
Section on Immunology and Immunogenetics, Joslin Diabetes Center, and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.
Proc Natl Acad Sci U S A. 2004 Nov 30;101(48):16885-90. doi: 10.1073/pnas.0407417101. Epub 2004 Nov 17.
Naïve T cells proliferate independently of cognate antigen when introduced into lymphopenic hosts. Lymphopenia-induced 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 antigen-independent proliferation; this process ultimately results in differentiation to "authentic" memory cells.
当被引入淋巴细胞减少的宿主时，初始T细胞可独立于同源抗原进行增殖。淋巴细胞减少诱导的增殖依赖于低亲和力的MHC/自身肽复合物以及白细胞介素-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细胞在转入淋巴细胞减少环境后不同时间点的基因表达变化。响应淋巴细胞减少而诱导的基因在很大程度上是由完全抗原刺激上调的基因的一个衰减子集，包括与细胞周期相关的基因，而不包括与效应器活性特异性相关的基因。在空的微环境中经历初始增殖阶段后，初始T细胞采用了一种与经历过抗原的记忆细胞相似的稳定基因表达模式。因此，在淋巴细胞减少的宿主中增殖的T细胞不会表现出独特的基因表达谱，而是依靠“传统”信号进行这种不依赖抗原的增殖；这一过程最终导致分化为“真正的”记忆细胞。
