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

Maldonado-López R, De Smedt T, Michel P, Godfroid J, Pajak B, Heirman C, Thielemans K, Leo O, Urbain J, Moser M - J. Exp. Med. (1999)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Département de Biologie Moléculaire, Université Libre de Bruxelles, B-1640 Rhode-Saint-Genèse, Belgium.

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. 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.

Show MeSH

Related in: MedlinePlus

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.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2192907&req=5

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.

Mentions: DCs were purified from spleens, pulsed with KLH during overnight culture (6), and further separated according to CD8α expression by FACS® sorting or by positive/negative selection on MACS®. Reanalysis of the sorted cell populations confirmed purity >99% (FACS®) or 97% (MACS®). 3 × 105 DCs were injected into the hind footpads of syngeneic mice, and the popliteal LNs were harvested 5 d later. The data in Fig. 1 a indicate that administration of purified CD8α+ or CD8α− DCs, or both, loaded ex vivo with antigen, resulted in T cell priming, as assessed by KLH-dependent proliferation in culture. The proliferative response of LN cells from mice injected with CD8α+ DCs was consistently higher compared with animals primed with CD8α− DCs. T cell priming was prevented by treatment of mice with neutralizing anti-CD4 mAbs, showing that the KLH-specific response was dependent on CD4+ T lymphocytes.


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

Maldonado-López R, De Smedt T, Michel P, Godfroid J, Pajak B, Heirman C, Thielemans K, Leo O, Urbain J, Moser M - J. Exp. Med. (1999)

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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2192907&req=5

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.
Mentions: DCs were purified from spleens, pulsed with KLH during overnight culture (6), and further separated according to CD8α expression by FACS® sorting or by positive/negative selection on MACS®. Reanalysis of the sorted cell populations confirmed purity >99% (FACS®) or 97% (MACS®). 3 × 105 DCs were injected into the hind footpads of syngeneic mice, and the popliteal LNs were harvested 5 d later. The data in Fig. 1 a indicate that administration of purified CD8α+ or CD8α− DCs, or both, loaded ex vivo with antigen, resulted in T cell priming, as assessed by KLH-dependent proliferation in culture. The proliferative response of LN cells from mice injected with CD8α+ DCs was consistently higher compared with animals primed with CD8α− DCs. T cell priming was prevented by treatment of mice with neutralizing anti-CD4 mAbs, showing that the KLH-specific response was dependent on CD4+ T lymphocytes.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Département de Biologie Moléculaire, Université Libre de Bruxelles, B-1640 Rhode-Saint-Genèse, Belgium.

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. 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.

Show MeSH
Related in: MedlinePlus