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

Heather D. Hickman, Lily Li, Glennys V. Reynoso, Erica J. Rubin, Cara N. Skon, Jacqueline W. Mays, James Gibbs, Owen Schwartz, Jack R. Bennink, Jonathan W. Yewdell

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

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 (V V), 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. V V 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, virusinduced chemokines in DLNs enable antiviral CD8 + T cells to distinguish DCs from macrophages to optimize T cell priming.

Original languageEnglish (US)
Pages (from-to)2511-2524
Number of pages14
JournalJournal of Experimental Medicine
Volume208
Issue number12
DOIs
StatePublished - Nov 21 2011

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