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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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CD1c-reactive T cells induce functional DC maturation. (A) Decreased uptake of soluble FITC dextran by mature DCs. Immature DCs were cultured in the presence of TNF-α (50 ng/ml), γ/δ clone JR.2 (T cell:DC ratio = 1:9), or medium alone for 48 h. These DCs were then washed and cultured in the presence of FITC–dextran during a 60 min time course and antigen uptake was assessed by flow cytometry. Note that DCs matured in the presence of clone JR.2 or TNFα had decreased uptake of FITC–dextran consistent with functional maturation. Open squares, medium; filled squares, JR.2; triangles, TNF-α. (B) Redistribution of MHC class II molecules in maturing DCs. Confocal microscopy was performed on DCs matured in the presence of TNF-α, JR.2 (T cell:DC ratio = 1:9) or medium alone. Cells were labeled with mAb against MHC class II (green staining) and the lysosomal marker LAMP 1 (red staining). Colocalization of these molecules is represented by the merged image (yellow). Note that DCs matured in the presence of JR.2 or TNF-α have increased staining of cell surface MHC class II and minimal colocalization with LAMP 1. Bar = 2 μm. (C) DC expression of cell surface CD83. DCs cultured in the presence of TNF-α or JR.2 expressed increased levels of the maturation marker CD83 as assessed by mAb staining and flow cytometry. These results are representative of three independent experiments using different DC donors.
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fig3: CD1c-reactive T cells induce functional DC maturation. (A) Decreased uptake of soluble FITC dextran by mature DCs. Immature DCs were cultured in the presence of TNF-α (50 ng/ml), γ/δ clone JR.2 (T cell:DC ratio = 1:9), or medium alone for 48 h. These DCs were then washed and cultured in the presence of FITC–dextran during a 60 min time course and antigen uptake was assessed by flow cytometry. Note that DCs matured in the presence of clone JR.2 or TNFα had decreased uptake of FITC–dextran consistent with functional maturation. Open squares, medium; filled squares, JR.2; triangles, TNF-α. (B) Redistribution of MHC class II molecules in maturing DCs. Confocal microscopy was performed on DCs matured in the presence of TNF-α, JR.2 (T cell:DC ratio = 1:9) or medium alone. Cells were labeled with mAb against MHC class II (green staining) and the lysosomal marker LAMP 1 (red staining). Colocalization of these molecules is represented by the merged image (yellow). Note that DCs matured in the presence of JR.2 or TNF-α have increased staining of cell surface MHC class II and minimal colocalization with LAMP 1. Bar = 2 μm. (C) DC expression of cell surface CD83. DCs cultured in the presence of TNF-α or JR.2 expressed increased levels of the maturation marker CD83 as assessed by mAb staining and flow cytometry. These results are representative of three independent experiments using different DC donors.

Mentions: We first investigated the ability of DCs matured in the presence of CD1c-reactive γ/δ T cells to internalize soluble antigens. After a 48-h culture with γ/δ clone JR.2 (T cell:DC ratio = 1:9), TNF-α (50 ng/ml), or medium alone, DCs were assessed for their ability to internalize the soluble fluorescent antigen FITC–Dextran (MW = 40,000; 1 mg/ml concentration) during a 60-min time course. DCs cultured in the presence of JR.2 (MFI = 132) or TNF-α (MFI = 100) showed decreased uptake of FITC–Dextran at 60 min when compared with immature DC cultured in medium alone (MFI = 369), consistent with their functional maturation (Fig. 3 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)

CD1c-reactive T cells induce functional DC maturation. (A) Decreased uptake of soluble FITC dextran by mature DCs. Immature DCs were cultured in the presence of TNF-α (50 ng/ml), γ/δ clone JR.2 (T cell:DC ratio = 1:9), or medium alone for 48 h. These DCs were then washed and cultured in the presence of FITC–dextran during a 60 min time course and antigen uptake was assessed by flow cytometry. Note that DCs matured in the presence of clone JR.2 or TNFα had decreased uptake of FITC–dextran consistent with functional maturation. Open squares, medium; filled squares, JR.2; triangles, TNF-α. (B) Redistribution of MHC class II molecules in maturing DCs. Confocal microscopy was performed on DCs matured in the presence of TNF-α, JR.2 (T cell:DC ratio = 1:9) or medium alone. Cells were labeled with mAb against MHC class II (green staining) and the lysosomal marker LAMP 1 (red staining). Colocalization of these molecules is represented by the merged image (yellow). Note that DCs matured in the presence of JR.2 or TNF-α have increased staining of cell surface MHC class II and minimal colocalization with LAMP 1. Bar = 2 μm. (C) DC expression of cell surface CD83. DCs cultured in the presence of TNF-α or JR.2 expressed increased levels of the maturation marker CD83 as assessed by mAb staining and flow cytometry. These results are representative of three independent experiments using different DC donors.
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Related In: Results  -  Collection

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fig3: CD1c-reactive T cells induce functional DC maturation. (A) Decreased uptake of soluble FITC dextran by mature DCs. Immature DCs were cultured in the presence of TNF-α (50 ng/ml), γ/δ clone JR.2 (T cell:DC ratio = 1:9), or medium alone for 48 h. These DCs were then washed and cultured in the presence of FITC–dextran during a 60 min time course and antigen uptake was assessed by flow cytometry. Note that DCs matured in the presence of clone JR.2 or TNFα had decreased uptake of FITC–dextran consistent with functional maturation. Open squares, medium; filled squares, JR.2; triangles, TNF-α. (B) Redistribution of MHC class II molecules in maturing DCs. Confocal microscopy was performed on DCs matured in the presence of TNF-α, JR.2 (T cell:DC ratio = 1:9) or medium alone. Cells were labeled with mAb against MHC class II (green staining) and the lysosomal marker LAMP 1 (red staining). Colocalization of these molecules is represented by the merged image (yellow). Note that DCs matured in the presence of JR.2 or TNF-α have increased staining of cell surface MHC class II and minimal colocalization with LAMP 1. Bar = 2 μm. (C) DC expression of cell surface CD83. DCs cultured in the presence of TNF-α or JR.2 expressed increased levels of the maturation marker CD83 as assessed by mAb staining and flow cytometry. These results are representative of three independent experiments using different DC donors.
Mentions: We first investigated the ability of DCs matured in the presence of CD1c-reactive γ/δ T cells to internalize soluble antigens. After a 48-h culture with γ/δ clone JR.2 (T cell:DC ratio = 1:9), TNF-α (50 ng/ml), or medium alone, DCs were assessed for their ability to internalize the soluble fluorescent antigen FITC–Dextran (MW = 40,000; 1 mg/ml concentration) during a 60-min time course. DCs cultured in the presence of JR.2 (MFI = 132) or TNF-α (MFI = 100) showed decreased uptake of FITC–Dextran at 60 min when compared with immature DC cultured in medium alone (MFI = 369), consistent with their functional maturation (Fig. 3 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