It is uncertain how antiviral lymphocytes are activated in draining lymph nodes, the site where adaptive immune responses are initiated. Here, using intravital microscopy we show that after infection of mice with vaccinia virus (a large DNA virus) or vesicular stomatitis virus (a small RNA virus), virions drained to the lymph node and infected cells residing just beneath the subcapsular sinus. Naive CD8+ T cells rapidly migrated to infected cells in the peripheral interfollicular region and then formed tight interactions with dendritic cells, leading to complete T cell activation. Thus, antigen presentation at the lymph node periphery, not at lymphocyte exit sites in deeper lymph node venules, as dogma dictates, has a dominant function in antiviral CD8+ T cell activation.
Bibliographical noteFunding Information:
We thank O. Schwartz, M. Czapiga, J. Kabat and S. Han for imaging advice and insight; D. Tokarchick and K. Irvine for technical assistance; and the staff of the Comparative Medical Branch of the National Institute of Allergy and Infectious Diseases (building 33) for animal care. Supported by the Intramural Research Program of National Institute of Allergy and Infectious Diseases.