A closer look at homeostatic proliferation of CD4+ T cells:: Costimulatory requirements and role in memory formation
A closer look at homeostatic proliferation of CD4+ T cells:: Costimulatory requirements and role in memory formation
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DOI：
10.4049/jimmunol.167.7.3699
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发表时间：
2001-10-01
影响因子：
4.4
通讯作者：
Turka, LA
中科院分区：
文献类型：
--
作者：
Gudmundsdottir, H;Turka, LA
Ag特异性CD 4（+）T细胞增殖部分受CD 28共刺激信号调节。初级激活期间的增殖反应是T细胞对抗原重新相遇做出反应的能力的重要决定因素。淋巴细胞减少症期间成熟CD 4（+）T细胞的增殖（稳态增殖）需要与内源性肽MHC相互作用。然而，共刺激在稳态增殖过程中的作用尚不清楚，稳态增殖调节次级T细胞反应的能力也不清楚。使用TCR转基因系统和连续过继转移，我们发现过继转移到重组激活基因（RAG）（-/-）受体后，CD 4（+）T细胞的稳态增殖发生至少5周。可以分辨两个离散的增殖T细胞群体，一个是高度增殖和依赖于CD 28信号传导的，另一个包含经历低水平的CD 28非依赖性增殖的细胞。重要的是，经历了稳态增殖的初始CD 4（+）T细胞获得了真正记忆细胞的表型和功能特征。这些研究表明，功能性记忆T细胞可以通过仅与内源性Ag相遇来产生。这种T细胞再生机制可能在由于病毒感染（如HIV）、移植或癌症治疗导致的淋巴细胞减少症期间活跃，并可能解释某些自身免疫性疾病。
Ag-specific proliferation of CD4(+) T cells is regulated, in part, by costimulatory signals through CD28. The proliferative response during primary activation is an important determinant of the ability of the T cell to respond to Ag re-encounter. Proliferation of mature CD4(+) T cells during lymphopenia (homeostatic proliferation) requires interaction with endogenous peptide MHC. However, the role of costimulation during homeostatic proliferation is unclear, as is the ability of homeostatic proliferation to regulate secondary T cell responses. Using a TCR transgenic system and serial adoptive transfers we find that homeostatic proliferation of CD4(+) T cells occurs for at least 5 wk after adoptive transfer into recombination-activating gene (RAG)(-/-) recipients. Two discrete populations of proliferating T cells can be resolved, one that is highly proliferative and dependent on CD28 signaling, and the other that contains cells undergoing low levels of CD28-independent proliferation. Importantly, naive CD4(+) T cells that have undergone homeostatic proliferation acquire both phenotypic and functional characteristics of true memory cells. These studies indicate that functional memory T cells can be generated by encounters with endogenous Ags only. This mechanism of T cell regeneration is possibly active during lymphopenia due to viral infections, such as HIV, transplantation, or cancer therapy, and may explain selected autoimmune diseases.