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. |