CD4+ T cells support cytotoxic T lymphocyte priming by controlling lymph node input
CD4+ T cells support cytotoxic T lymphocyte priming by controlling lymph node input
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DOI：
10.1073/pnas.1100567108
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发表时间：
2011-05-24
影响因子：
11.1
通讯作者：
Iwasaki, Akiko
中科院分区：
文献类型：
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作者：
Kumamoto, Yosuke;Mattei, Lisa M.;Iwasaki, Akiko
快速诱导CD8（+）细胞毒性T淋巴细胞（CTL）应答对于对抗细胞内病原体的急性感染至关重要。CD4（+）T细胞在外周感染后帮助引发次级淋巴器官中的抗原特异性CTL。虽然幼稚前体的频率非常低，但免疫系统能够通过尚不清楚的机制有效地筛选同源CTL。在这里，我们研究了CD4（+）T细胞在免疫反应早期阶段的作用。我们发现，CD4（+）T细胞通过促进初始多克隆CD8（+）T细胞在感染或免疫后早期进入引流淋巴结（dLN），有助于最佳的CTL扩增。CD4（+）T细胞也促进幼稚B细胞输入反应性LN。这种“帮助”包括通过树突状细胞的活化来扩张供给dLN的小动脉和扩大dLN。以抗原和CD40依赖的方式，CD4（+）T细胞激活树突状细胞以支持幼稚淋巴细胞向dLN募集。我们的研究结果揭示了一种以前未被重视的CD4（+）T细胞帮助模式，从而增加了幼稚淋巴细胞对相关LN的输入，以有效筛选同源CD8（+）T细胞。
Rapid induction of CD8(+) cytotoxic T lymphocyte (CTL) responses is critical to combat acute infection with intracellular pathogens. CD4(+) T cells help prime antigen-specific CTLs in secondary lymphoid organs after infection in the periphery. Although the frequency of naive precursors is very low, the immune system is able to efficiently screen for cognate CTLs through mechanisms that are not well understood. Here we examine the role of CD4(+) T cells in early phases of the immune response. We show that CD4(+) T cells help optimal CTL expansion by facilitating entry of naive polyclonal CD8(+) T cells into the draining lymph node (dLN) early after infection or immunization. CD4(+) T cells also facilitate input of naive B cells into reactive LNs. Such "help" involves expansion of the arteriole feeding the dLN and enlargement of the dLN through activation of dendritic cells. In an antigen-and CD40-dependent manner, CD4(+) T cells activate dendritic cells to support naive lymphocyte recruitment to the dLN. Our results reveal a previously unappreciated mode of CD4(+) T-cell help, whereby they increase the input of naive lymphocytes to the relevant LN for efficient screening of cognate CD8(+) T cells.