Robust Anti-viral Immunity Requires Multiple Distinct T Cell-Dendritic Cell Interactions

Cell. 2015 Sep 10;162(6):1322-37. doi: 10.1016/j.cell.2015.08.004. Epub 2015 Aug 18.


Host defense against viruses and intracellular parasites depends on effector CD8(+) T cells, whose optimal clonal expansion, differentiation, and memory properties require signals from CD4(+) T cells. Here, we addressed the role of dendritic cell (DC) subsets in initial activation of the two T cell types and their co-operation. Surprisingly, initial priming of CD4(+) and CD8(+) T cells was spatially segregated within the lymph node and occurred on different DCs with temporally distinct patterns of antigen presentation via MHCI versus MHCII molecules. DCs that co-present antigen via both MHC molecules were detected at a later stage; these XCR1(+) DCs are the critical platform involved in CD4(+) T cell augmentation of CD8(+) T cell responses. These findings delineate the complex choreography of cellular interactions underlying effective cell-mediated anti-viral responses, with implications for basic DC subset biology, as well as for translational application to the development of vaccines that evoke optimal T cell immunity.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, Viral / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Communication*
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Mice
  • Receptors, Chemokine / genetics
  • Spleen / cytology
  • Spleen / immunology
  • Vaccinia / immunology*
  • Vaccinia virus / physiology*


  • Antigens, Viral
  • Receptors, Chemokine
  • XC chemokine receptor 1, mouse