Mouse lung CD103+ and CD11bhigh dendritic cells preferentially induce distinct CD4+ T-cell responses

Kazuki Furuhashi, Takafumi Suda, Hirotsugu Hasegawa, Yuzo Suzuki, Dai Hashimoto, Noriyuki Enomoto, Tomoyuki Fujisawa, Yutaro Nakamura, Naoki Inui, Kiyoshi Shibata, Hirotoshi Nakamura, Kingo Chida
American Journal of Respiratory Cell and Molecular Biology 2012, 46 (2): 165-72
Mouse lung dendritic cells (LDCs) have been recently shown to contain two major subpopulations: CD103(+) CD11b(low or negative) (CD103(+) LDCs) and CD103(-) CD11b(high) LDCs (CD11b(high) LDCs). Although several studies have demonstrated functional differences between them, it is unclear whether the subpopulations induce distinct T helper (Th) cell responses. The present study was conducted to examine whether CD103(+) and CD11b(high) LDCs preferentially generate different Th responses. Naive DO11.10 CD4(+) T cells were primed with CD103(+) or CD11b(high) LDCs obtained from normal BALB/c mice. The primed CD4(+) T cells were restimulated, and their cytokine secretions were assessed. The expression of intracellular cytokines and the mRNA levels of chemokine receptors were also measured. We found that the CD4(+) T cells primed with CD103(+) LDCs secreted significantly larger amounts of IFN-γ and IL-17A, whereas those primed with CD11b(high) LDCs released significantly higher levels of IL-4, IL-6, and IL-10. Intracellular cytokine assay showed that CD103(+) LDCs induced greater frequencies of CD4(+) T cells producing IFN-γ and IL-17A, whereas CD11b(high) LDCs were more efficient at inducing CD4(+) T cells producing IL-4 and IL-10. The mRNA levels of CXCR3 and CCR5, which are expressed preferentially in Th1 cells, were significantly higher in CD4(+) T cells primed with CD103(+) LDCs. The mRNA levels of CXCR4 and CCR4, which are expressed primarily in Th2 cells, were significantly greater in those primed with CD11b(high) LDCs. These data suggest that mouse CD103(+) LDCs predominantly elicit Th1 and Th17 responses, whereas CD11b(high) LDCs primarily provoke a Th2 response under the steady state.

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