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Publication : Chemokines control naive CD8+ T cell selection of optimal lymph node antigen presenting cells.

First Author  Hickman HD Year  2011
Journal  J Exp Med Volume  208
Issue  12 Pages  2511-24
PubMed ID  22042976 Mgi Jnum  J:178641
Mgi Id  MGI:5299394 Doi  10.1084/jem.20102545
Citation  Hickman HD, et al. (2011) Chemokines control naive CD8+ T cell selection of optimal lymph node antigen presenting cells. J Exp Med 208(12):2511-24
abstractText  Naive antiviral CD8(+) T cells are activated in the draining LN (DLN) by dendritic cells (DCs) presenting viral antigens. However, many viruses infect LN macrophages, which participate in initiation of innate immunity and B cell activation. To better understand how and why T cells select infected DCs rather than macrophages, we performed intravital microscopy and ex vivo analyses after infecting mice with vaccinia virus (VV), a large DNA virus that infects both LN macrophages and DCs. Although CD8(+) T cells interact with both infected macrophages and DCs in the LN peripheral interfollicular region (PIR), DCs generate more frequent and stable interactions with T cells. VV infection induces rapid release of CCR5-binding chemokines in the LN, and administration of chemokine-neutralizing antibodies diminishes T cell activation by increasing T cell localization to macrophages in the macrophage-rich region (MRR) at the expense of PIR DCs. Similarly, DC ablation increases both T cell localization to the MRR and the duration of T cell-macrophage contacts, resulting in suboptimal T cell activation. Thus, virus-induced chemokines in DLNs enable antiviral CD8(+) T cells to distinguish DCs from macrophages to optimize T cell priming.
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