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. 1999 Feb 1;189(3):587-92.
doi: 10.1084/jem.189.3.587.

CD8alpha+ and CD8alpha- subclasses of dendritic cells direct the development of distinct T helper cells in vivo

R Maldonado-López  1 , T De Smedt, P Michel, J Godfroid, B Pajak, C Heirman, K Thielemans, O Leo, J Urbain, M Moser
Affiliations

VSports手机版 - CD8alpha+ and CD8alpha- subclasses of dendritic cells direct the development of distinct T helper cells in vivo

R Maldonado-López (V体育ios版) et al. J Exp Med. .

Abstract

Cells of the dendritic family display some unique properties that confer to them the capacity to sensitize naive T cells in vitro and in vivo. In the mouse, two subclasses of dendritic cells (DCs) have been described that differ by their CD8alpha expression and their localization in lymphoid organs. The physiologic function of both cell populations remains obscure. Studies conducted in vitro have suggested that CD8alpha+ DCs could play a role in the regulation of immune responses, whereas conventional CD8alpha- DCs would be more stimulatory VSports手机版. We report here that both subclasses of DCs efficiently prime antigen-specific T cells in vivo, and direct the development of distinct T helper (Th) populations. Antigen-pulsed CD8alpha+ and CD8alpha- DCs are separated after overnight culture in recombinant granulocyte/macrophage colony-stimulating factor and injected into the footpads of syngeneic mice. Administration of CD8alpha- DCs induces a Th2-type response, whereas injection of CD8alpha+ DCs leads to Th1 differentiation. We further show that interleukin 12 plays a critical role in Th1 development by CD8alpha+ DCs. These findings suggest that the nature of the DC that presents the antigen to naive T cells may dictate the class selection of the adaptative immune response. .

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Figures

Figure 1
Figure 1
CD8α+ and CD8α− DCs prime distinct Th cells in vivo. LN cells from mice injected with either subset or a combination (at a proportion of 1 CD8α+ to 10 CD8α−) 5 d earlier were cultured without antigen or with 50 (a) or 10 (a–f) μg/ml KLH. Some mice were injected with 1 mg anti-CD4 mAbs before priming. Proliferation and lymphokine production were measured as indicated in Materials and Methods. Figure summarizes the results (mean ± SD) obtained in five independent experiments.
Figure 2
Figure 2
CD8α+ and CD8α− DCs induce distinct memory responses in vivo. Balb/c mice were either left untreated (I) or were primed with KLH-pulsed CD8α+, CD8α−, or the combination 14 d earlier, and boosted with unseparated DCs, pulsed with the same antigen. LN cells were harvested 2 d later and cultured with (a) graded doses or (b–f) 10 μg/ml KLH. Proliferation (a) and lymphokine production (b–f) were measured as indicated in Materials and Methods. Figure summarizes the results (mean ± SD) obtained in four independent experiments.
Figure 3
Figure 3
The priming of Th1 cells by CD8α+ DCs is IL-12 dependent. (a and b) CD8α+ or CD8α− DCs or both subsets, isolated from p40-deficient (KO) or wild-type (WT) mice, were loaded with KLH and injected into the footpads of Balb/c mice. (c and d) Balb/c mice were injected in the footpads with CD8α+ or CD8α− DCs with or without four daily injections of 200 ng i.p. rmIL-12. LN cells were harvested 5 d later and cultured with 10 μg/ml antigen. The production of IFN-γ and IL-4 was measured in the supernatants, as indicated in Materials and Methods. Similar data were obtained in all four experiments performed.
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