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CD1-mediated gamma/delta T cell maturation of dendritic cells.

Leslie DS, Vincent MS, Spada FM, Das H, Sugita M, Morita CT, Brenner MB - J. Exp. Med. (2002)

Bottom Line: In addition, these DCs were able to efficiently present peptide antigens to naive CD4+ T cells.CD1-restricted gamma/delta T cell recognition of immature DCs provides the human immune system with the capacity to rapidly generate a pool of mature DCs early during microbial invasion.This may be an important source of critical host signals for T helper type 1 polarization of antigen-specific naive T cells and the subsequent adaptive immune response.

View Article: PubMed Central - PubMed

Affiliation: Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital at Harvard Medical School, Boston, MA 02115, USA.

ABSTRACT
Immature myeloid dendritic cells (DCs) express only low levels of major histocompatibility complex (MHC) class II but express high levels of CD1 a, b, and c antigen-presenting molecules at the cell surface. As Vdelta1+ gamma/delta T cells are the main tissue subset of gamma/delta T cells and they are known to recognize CD1c in the absence of specific foreign antigen recognition, we examined the possible interaction of these T cells with immature DCs. We show that CD1-restricted gamma/delta T cells can mediate the maturation of DCs. DC maturation required cell-cell contact and could be blocked by antibodies against CD1c. The maturation process was partially mediated by tumor necrosis factor alpha. Importantly, immature DCs matured in the presence of lipopolysaccharide and CD1-restricted gamma/delta T cells produced bioactive interleukin-12p70. In addition, these DCs were able to efficiently present peptide antigens to naive CD4+ T cells. CD1-restricted gamma/delta T cell recognition of immature DCs provides the human immune system with the capacity to rapidly generate a pool of mature DCs early during microbial invasion. This may be an important source of critical host signals for T helper type 1 polarization of antigen-specific naive T cells and the subsequent adaptive immune response.

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CD1-restricted γ/δ T cells induce phenotypic DC maturation. (A) Immature monocyte-derived DCs cultured with Vδ1+ CD1-restricted T cell clones JR.2 and XV.1 for 48 h expressed increased CD83 and CD86 cell surface molecules when compared with DCs cultured in medium alone as assessed by mAb staining and flow cytometry. (B) Immature DCs cultured with CD1c-restricted γ/δ clone JR.2 or TNF-α (50 ng/ml) for 48 h expressed increased levels of CD83 and CD86 cell surface molecules. Culture of DCs with Vδ1+ clones 10G4, 20H8, and a Vδ2+ γ/δ line (which are not CD1-restricted) all failed to promote maturation of DCs as assessed by CD83 and CD86 cell surface expression. Open squares, medium alone; open triangles, TNF-α, filled squares, JR.2; diamonds, XV.1; triangles, 10G4; inverted triangles, 20H8; circles, Vδ2 line. These results are representative of four independent experiments using different DC donors.
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fig1: CD1-restricted γ/δ T cells induce phenotypic DC maturation. (A) Immature monocyte-derived DCs cultured with Vδ1+ CD1-restricted T cell clones JR.2 and XV.1 for 48 h expressed increased CD83 and CD86 cell surface molecules when compared with DCs cultured in medium alone as assessed by mAb staining and flow cytometry. (B) Immature DCs cultured with CD1c-restricted γ/δ clone JR.2 or TNF-α (50 ng/ml) for 48 h expressed increased levels of CD83 and CD86 cell surface molecules. Culture of DCs with Vδ1+ clones 10G4, 20H8, and a Vδ2+ γ/δ line (which are not CD1-restricted) all failed to promote maturation of DCs as assessed by CD83 and CD86 cell surface expression. Open squares, medium alone; open triangles, TNF-α, filled squares, JR.2; diamonds, XV.1; triangles, 10G4; inverted triangles, 20H8; circles, Vδ2 line. These results are representative of four independent experiments using different DC donors.

Mentions: Outside the thymus, only myeloid dendritic cells are known to express all of the group I (CD1a, CD1b, and CD1c) and group2 (CD1d) CD1 isoforms (9). As we had previously isolated human γ/δ T cells expressing Vδ1 TCRs that recognize CD1c in the absence of exogenous microbial antigens (13), we hypothesized that this T cell population might mediate the maturation of immature monocyte-derived dendritic cells. Fresh blood monocytes were cultured with GM-CSF and IL-4 for 2 to 3 d, in vitro, to obtain a pool of immature monocyte-derived DCs. Cocultures of such DCs with CD1-reactive γ/δ T cells clones resulted in increased cell surface expression of the costimulatory molecule CD86 (B7.2) and an increased percentage of cells expressing the maturation marker CD83, consistent with DC maturation. For example, culture of the CD1c-restricted γ/δ T clones JR.2 and XV.1 with immature DCs at ratios ranging from 1:3 to 1:27 T cells per DC for 48 h led to a 9- and 13-fold increase in DC cell surface expression of CD86 for JR.2 and XV.1, respectively (from MFI = 196.7 to MFI = 2,565.1 for JR.2 and MFI = 1,742.6 for XV.1), as well as an increase in the percentage of CD83+ DCs (from 3.5 to 75.5% for JR.2 and 61.7% for XV.1) when compared with DCs cultured in medium alone. (Fig. 1 A).


CD1-mediated gamma/delta T cell maturation of dendritic cells.

Leslie DS, Vincent MS, Spada FM, Das H, Sugita M, Morita CT, Brenner MB - J. Exp. Med. (2002)

CD1-restricted γ/δ T cells induce phenotypic DC maturation. (A) Immature monocyte-derived DCs cultured with Vδ1+ CD1-restricted T cell clones JR.2 and XV.1 for 48 h expressed increased CD83 and CD86 cell surface molecules when compared with DCs cultured in medium alone as assessed by mAb staining and flow cytometry. (B) Immature DCs cultured with CD1c-restricted γ/δ clone JR.2 or TNF-α (50 ng/ml) for 48 h expressed increased levels of CD83 and CD86 cell surface molecules. Culture of DCs with Vδ1+ clones 10G4, 20H8, and a Vδ2+ γ/δ line (which are not CD1-restricted) all failed to promote maturation of DCs as assessed by CD83 and CD86 cell surface expression. Open squares, medium alone; open triangles, TNF-α, filled squares, JR.2; diamonds, XV.1; triangles, 10G4; inverted triangles, 20H8; circles, Vδ2 line. These results are representative of four independent experiments using different DC donors.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196072&req=5

fig1: CD1-restricted γ/δ T cells induce phenotypic DC maturation. (A) Immature monocyte-derived DCs cultured with Vδ1+ CD1-restricted T cell clones JR.2 and XV.1 for 48 h expressed increased CD83 and CD86 cell surface molecules when compared with DCs cultured in medium alone as assessed by mAb staining and flow cytometry. (B) Immature DCs cultured with CD1c-restricted γ/δ clone JR.2 or TNF-α (50 ng/ml) for 48 h expressed increased levels of CD83 and CD86 cell surface molecules. Culture of DCs with Vδ1+ clones 10G4, 20H8, and a Vδ2+ γ/δ line (which are not CD1-restricted) all failed to promote maturation of DCs as assessed by CD83 and CD86 cell surface expression. Open squares, medium alone; open triangles, TNF-α, filled squares, JR.2; diamonds, XV.1; triangles, 10G4; inverted triangles, 20H8; circles, Vδ2 line. These results are representative of four independent experiments using different DC donors.
Mentions: Outside the thymus, only myeloid dendritic cells are known to express all of the group I (CD1a, CD1b, and CD1c) and group2 (CD1d) CD1 isoforms (9). As we had previously isolated human γ/δ T cells expressing Vδ1 TCRs that recognize CD1c in the absence of exogenous microbial antigens (13), we hypothesized that this T cell population might mediate the maturation of immature monocyte-derived dendritic cells. Fresh blood monocytes were cultured with GM-CSF and IL-4 for 2 to 3 d, in vitro, to obtain a pool of immature monocyte-derived DCs. Cocultures of such DCs with CD1-reactive γ/δ T cells clones resulted in increased cell surface expression of the costimulatory molecule CD86 (B7.2) and an increased percentage of cells expressing the maturation marker CD83, consistent with DC maturation. For example, culture of the CD1c-restricted γ/δ T clones JR.2 and XV.1 with immature DCs at ratios ranging from 1:3 to 1:27 T cells per DC for 48 h led to a 9- and 13-fold increase in DC cell surface expression of CD86 for JR.2 and XV.1, respectively (from MFI = 196.7 to MFI = 2,565.1 for JR.2 and MFI = 1,742.6 for XV.1), as well as an increase in the percentage of CD83+ DCs (from 3.5 to 75.5% for JR.2 and 61.7% for XV.1) when compared with DCs cultured in medium alone. (Fig. 1 A).

Bottom Line: In addition, these DCs were able to efficiently present peptide antigens to naive CD4+ T cells.CD1-restricted gamma/delta T cell recognition of immature DCs provides the human immune system with the capacity to rapidly generate a pool of mature DCs early during microbial invasion.This may be an important source of critical host signals for T helper type 1 polarization of antigen-specific naive T cells and the subsequent adaptive immune response.

View Article: PubMed Central - PubMed

Affiliation: Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital at Harvard Medical School, Boston, MA 02115, USA.

ABSTRACT
Immature myeloid dendritic cells (DCs) express only low levels of major histocompatibility complex (MHC) class II but express high levels of CD1 a, b, and c antigen-presenting molecules at the cell surface. As Vdelta1+ gamma/delta T cells are the main tissue subset of gamma/delta T cells and they are known to recognize CD1c in the absence of specific foreign antigen recognition, we examined the possible interaction of these T cells with immature DCs. We show that CD1-restricted gamma/delta T cells can mediate the maturation of DCs. DC maturation required cell-cell contact and could be blocked by antibodies against CD1c. The maturation process was partially mediated by tumor necrosis factor alpha. Importantly, immature DCs matured in the presence of lipopolysaccharide and CD1-restricted gamma/delta T cells produced bioactive interleukin-12p70. In addition, these DCs were able to efficiently present peptide antigens to naive CD4+ T cells. CD1-restricted gamma/delta T cell recognition of immature DCs provides the human immune system with the capacity to rapidly generate a pool of mature DCs early during microbial invasion. This may be an important source of critical host signals for T helper type 1 polarization of antigen-specific naive T cells and the subsequent adaptive immune response.

Show MeSH
Related in: MedlinePlus