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

J Exp Med. 2011 Nov 21;208(12):2511-24. doi: 10.1084/jem.20102545. Epub 2011 Oct 31.

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 (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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Chemokines / immunology*
  • Chemokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / virology
  • Histocytochemistry
  • Lymph Nodes / cytology*
  • Lymph Nodes / immunology
  • Lymphocyte Activation / immunology*
  • Macrophages / virology
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • Receptors, CCR5 / metabolism
  • Vaccinia virus / immunology

Substances

  • Antigens, Viral
  • Chemokines
  • Receptors, CCR5