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CD40 ligation on human cord blood CD34+ hematopoietic progenitors induces their proliferation and differentiation into functional dendritic cells.

Flores-Romo L, Björck P, Duvert V, van Kooten C, Saeland S, Banchereau J - J. Exp. Med. (1997)

Bottom Line: DC generated via the CD40 pathway displayed strong major histocompatibility complex class II DR but lacked detectable CD1a and CD40 expression.These features were shared by a dendritic population identified in situ in tonsillar T cell areas.Taken together, the present data demonstrate that CD40 is functional on CD34HPC and its cross-linking by CD40L+ cells results in the generation of DC that may prime immune reactions during antigen-driven responses to pathogenic invasion, thus providing a link between hematopoiesis, innate, and adaptive immunity.

View Article: PubMed Central - PubMed

Affiliation: Schering-Plough, Laboratory for Immunological Research, Dardilly, France.

ABSTRACT
Human CD34+ multilineage progenitor cells (CD34HPC) from cord blood and bone marrow express CD40, a member of the tumor necrosis factor-receptor family present on various hematopoietic and nonhematopoietic cells. As hyper-IgM patients with mutated CD40 ligand (CD40L) exhibit neutropenia, no B cell memory, and altered T cell functions leading to severe infections, we investigated the potential role of CD40 on CD34HPC development. CD40-activated cord blood CD34HPC were found to proliferate and differentiate independently of granulocyte/macrophage colony-stimulating factor, into a cell population with prominent dendritic cell (DC) attributes including priming of allogeneic naive T cells. DC generated via the CD40 pathway displayed strong major histocompatibility complex class II DR but lacked detectable CD1a and CD40 expression. These features were shared by a dendritic population identified in situ in tonsillar T cell areas. Taken together, the present data demonstrate that CD40 is functional on CD34HPC and its cross-linking by CD40L+ cells results in the generation of DC that may prime immune reactions during antigen-driven responses to pathogenic invasion, thus providing a link between hematopoiesis, innate, and adaptive immunity.

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DC generated in the CD40L system stimulate primary T cell  responses. The functional capacity of CD40-generated DC was determined in a primary MLR culturing varying amounts of irradiated DC  with CD4+ cord blood T cells. DC obtained at day 14 as described were  irradiated and plated at different concentrations with 2 × 104 cord blood– derived CD4+ T cells prepared from a different donor by negative selection (see Materials and Methods). Stimulation of naive T cells is presented  as mean [3H]thymidine incorporation ± SD measured in triplicate wells  at day 5. Data are representative of three different experiments.
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Figure 4: DC generated in the CD40L system stimulate primary T cell responses. The functional capacity of CD40-generated DC was determined in a primary MLR culturing varying amounts of irradiated DC with CD4+ cord blood T cells. DC obtained at day 14 as described were irradiated and plated at different concentrations with 2 × 104 cord blood– derived CD4+ T cells prepared from a different donor by negative selection (see Materials and Methods). Stimulation of naive T cells is presented as mean [3H]thymidine incorporation ± SD measured in triplicate wells at day 5. Data are representative of three different experiments.

Mentions: DC, unlike monocytes or lymphocytes, display the unique property of vigorously stimulating the proliferation of naive T cells (28). As few as 300 CD40L-cultured CD34HPC were able to induce naive CD4+ cord blood T cells (ratio 1/66) to enter into DNA synthesis and 3,000 CD40L-derived DC (ratio 1/6.6) increased T cell thymidine incorporation by 250-fold (Fig. 4). In contrast, freshly isolated or IL-3-cultured CD34HPC are unable to induce naive T cell proliferation (1). Thus, in addition to their morphology, motility and phenotype, cells generated by CD40 ligation of CD34HPC possess the antigen-presenting capacity of DC.


CD40 ligation on human cord blood CD34+ hematopoietic progenitors induces their proliferation and differentiation into functional dendritic cells.

Flores-Romo L, Björck P, Duvert V, van Kooten C, Saeland S, Banchereau J - J. Exp. Med. (1997)

DC generated in the CD40L system stimulate primary T cell  responses. The functional capacity of CD40-generated DC was determined in a primary MLR culturing varying amounts of irradiated DC  with CD4+ cord blood T cells. DC obtained at day 14 as described were  irradiated and plated at different concentrations with 2 × 104 cord blood– derived CD4+ T cells prepared from a different donor by negative selection (see Materials and Methods). Stimulation of naive T cells is presented  as mean [3H]thymidine incorporation ± SD measured in triplicate wells  at day 5. Data are representative of three different experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196112&req=5

Figure 4: DC generated in the CD40L system stimulate primary T cell responses. The functional capacity of CD40-generated DC was determined in a primary MLR culturing varying amounts of irradiated DC with CD4+ cord blood T cells. DC obtained at day 14 as described were irradiated and plated at different concentrations with 2 × 104 cord blood– derived CD4+ T cells prepared from a different donor by negative selection (see Materials and Methods). Stimulation of naive T cells is presented as mean [3H]thymidine incorporation ± SD measured in triplicate wells at day 5. Data are representative of three different experiments.
Mentions: DC, unlike monocytes or lymphocytes, display the unique property of vigorously stimulating the proliferation of naive T cells (28). As few as 300 CD40L-cultured CD34HPC were able to induce naive CD4+ cord blood T cells (ratio 1/66) to enter into DNA synthesis and 3,000 CD40L-derived DC (ratio 1/6.6) increased T cell thymidine incorporation by 250-fold (Fig. 4). In contrast, freshly isolated or IL-3-cultured CD34HPC are unable to induce naive T cell proliferation (1). Thus, in addition to their morphology, motility and phenotype, cells generated by CD40 ligation of CD34HPC possess the antigen-presenting capacity of DC.

Bottom Line: DC generated via the CD40 pathway displayed strong major histocompatibility complex class II DR but lacked detectable CD1a and CD40 expression.These features were shared by a dendritic population identified in situ in tonsillar T cell areas.Taken together, the present data demonstrate that CD40 is functional on CD34HPC and its cross-linking by CD40L+ cells results in the generation of DC that may prime immune reactions during antigen-driven responses to pathogenic invasion, thus providing a link between hematopoiesis, innate, and adaptive immunity.

View Article: PubMed Central - PubMed

Affiliation: Schering-Plough, Laboratory for Immunological Research, Dardilly, France.

ABSTRACT
Human CD34+ multilineage progenitor cells (CD34HPC) from cord blood and bone marrow express CD40, a member of the tumor necrosis factor-receptor family present on various hematopoietic and nonhematopoietic cells. As hyper-IgM patients with mutated CD40 ligand (CD40L) exhibit neutropenia, no B cell memory, and altered T cell functions leading to severe infections, we investigated the potential role of CD40 on CD34HPC development. CD40-activated cord blood CD34HPC were found to proliferate and differentiate independently of granulocyte/macrophage colony-stimulating factor, into a cell population with prominent dendritic cell (DC) attributes including priming of allogeneic naive T cells. DC generated via the CD40 pathway displayed strong major histocompatibility complex class II DR but lacked detectable CD1a and CD40 expression. These features were shared by a dendritic population identified in situ in tonsillar T cell areas. Taken together, the present data demonstrate that CD40 is functional on CD34HPC and its cross-linking by CD40L+ cells results in the generation of DC that may prime immune reactions during antigen-driven responses to pathogenic invasion, thus providing a link between hematopoiesis, innate, and adaptive immunity.

Show MeSH
Related in: MedlinePlus