期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2011
卷号：108
期号：21
页码：8749-8754
DOI：10.1073/pnas.1100567108
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
