Mouse Lung CD103+ and CD11bhigh Dendritic Cells Preferentially Induce Distinct CD4+ T-Cell Responses

K Furuhashi, T Suda, H Hasegawa… - American journal of …, 2012 - atsjournals.org
K Furuhashi, T Suda, H Hasegawa, Y Suzuki, D Hashimoto, N Enomoto, T Fujisawa
American journal of respiratory cell and molecular biology, 2012atsjournals.org
Mouse lung dendritic cells (LDCs) have been recently shown to contain two major
subpopulations: CD103+ CD11blow or negative (CD103+ LDCs) and CD103− CD11bhigh
LDCs (CD11bhigh 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
CD11bhigh LDCs preferentially generate different Th responses. Naive DO11. 10 CD4+ T …
Mouse lung dendritic cells (LDCs) have been recently shown to contain two major subpopulations: CD103+ CD11blow or negative (CD103+ LDCs) and CD103 CD11bhigh LDCs (CD11bhigh 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 CD11bhigh LDCs preferentially generate different Th responses. Naive DO11.10 CD4+ T cells were primed with CD103+ or CD11bhigh 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 CD11bhigh 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 CD11bhigh 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 CD11bhigh LDCs. These data suggest that mouse CD103+ LDCs predominantly elicit Th1 and Th17 responses, whereas CD11bhigh LDCs primarily provoke a Th2 response under the steady state.
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