TY - JOUR
T1 - Chemokines control naive CD8 + T cell selection of optimal lymph node antigen presenting cells
AU - Hickman, Heather D.
AU - Li, Lily
AU - Reynoso, Glennys V.
AU - Rubin, Erica J.
AU - Skon, Cara N.
AU - Mays, Jacqueline W.
AU - Gibbs, James
AU - Schwartz, Owen
AU - Bennink, Jack R.
AU - Yewdell, Jonathan W.
PY - 2011/11/21
Y1 - 2011/11/21
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20102545
DO - 10.1084/jem.20102545
M3 - Article
C2 - 22042976
AN - SCOPUS:84862908259
SN - 0022-1007
VL - 208
SP - 2511
EP - 2524
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 12
ER -