Spatiotemporally Distinct Interactions with Dendritic Cell Subsets Facilitates CD4+ and CD8+ T Cell Activation to Localized Viral Infection

Immunity. 2015 Sep 15;43(3):554-65. doi: 10.1016/j.immuni.2015.07.020. Epub 2015 Aug 18.


The dynamics of when and where CD4(+) T cells provide help for CD8(+) T cell priming and which dendritic cells (DCs) activate CD4(+) T cells in vivo after localized infection are poorly understood. By using a cutaneous herpes simplex virus infection model combined with intravital 2-photon imaging of the draining lymph node (LN) to concurrently visualize pathogen-specific CD4(+) and CD8(+) T cells, we found that early priming of CD4(+) T cells involved clustering with migratory skin DCs. CD8(+) T cells did not interact with migratory DCs and their activation was delayed, requiring later clustering interactions with LN-resident XCR1(+) DCs. CD4(+) T cells interacted with these late CD8(+) T cell clusters on resident XCR1(+) DCs. Together, these data reveal asynchronous T cell activation by distinct DC subsets and highlight the key role of XCR1(+) DCs as the central platform for cytotoxic T lymphocyte activation and the delivery of CD4(+) T cell help.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Communication / immunology*
  • Cell Movement / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Fluorescent Dyes / chemistry
  • Herpes Simplex / immunology
  • Herpes Simplex / metabolism
  • Herpes Simplex / virology
  • Host-Pathogen Interactions / immunology
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology*
  • Lymph Nodes / virology
  • Lymphocyte Activation / immunology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Confocal
  • Microscopy, Fluorescence, Multiphoton
  • Receptors, Chemokine / immunology
  • Receptors, Chemokine / metabolism
  • Rhodamines / chemistry
  • Simplexvirus / immunology
  • Simplexvirus / physiology


  • Fluorescent Dyes
  • Receptors, Chemokine
  • Rhodamines
  • XC chemokine receptor 1, mouse
  • tetramethylrhodamine isothiocyanate