Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute T(H)1 immune responses

T(H)1-polarized immune responses, which confer protection against intracellular pathogens, are thought to be initiated by dendritic cells (DCs) that enter lymph nodes from peripheral tissues. We found following viral infection or immunization, inflammatory monocytes were recruited into lymph nodes directly from the blood to become CD11c(+)CD11b(hi)Gr-1(+) inflammatory DCs, which produced abundant interleukin 12(p70) and potently stimulated T(H)1 responses. This monocyte extravasation required CCR2 but not CCL2 or CCR7. Thus, inflammatory DC accumulation and T(H)1 responses were markedly reduced in Ccr2(−/−)mice, preserved in Ccl2(−/−) mice, and relatively increased in CCL19-CCL21-Ser-deficient plt mutant mice, in which all other lymph node DC types were reduced. We conclude that blood-derived inflammatory DCs play a major role in the development of T(H)1 immune responses.