Antigen-pulsed CD8α+ dendritic cells generate an immune response after subcutaneous injection without homing to the draining lymph node

Two subsets of murine splenic dendritic cells, derived from distinct precursors, can be distinguished by surface expression of CD8 alpha homodimers. The functions of the two subsets remain controversial, although it has been suggested that the lymphoid-derived (CD8 alpha(+)) subset induces tolerance, whereas the myeloid-derived (CD8 alpha(-)) subset has been shown to prime naive T cells and to generate memory responses. To study their capacity to prime or tolerize naive CD4(+) T cells in vivo, purified CD8 alpha(+) or CD8 alpha(-) dendritic cells were injected subcutaneously into normal mice. In contrast to CD8 alpha(-) dendl-itic cells, the CD8 alpha(+) fraction failed to traffic to the draining lymph node and did not generate responses to intravenous peptide However, after in vitro pulsing with peptide, strong in vivo T cell responses to purified CD8 alpha(+) dendritic cells could be detected. Such responses may have been initiated via transfer of peptide-major histocompatibility complex complexes to migratory host CD8 alpha(-) dendritic cells after injection. These data suggest that correlation of T helper cell type 1 (Th1) and Th2 priming with injection of CD8 alpha(+) and CD8 alpha(-) dendritic cells, respectively, may not result from direct T cell activation by lymphoid versus myeloid dendritic cells, but rather from indirect modification of the response to immunogenic CD8 alpha(-) dendritic cells by CD8 alpha(+) dendritic cells.