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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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IL-12p70 production by DCs requires both CD1-restricted γ/δ T cells and LPS. Immature DCs were incubated for 24 h with the JR.2 γ/δ T cell clone, LPS (10 ng/ml), or both JR.2 and LPS in the presence of blocking mAbs against IFN-γ, CD1c, or CD1a. The culture supernatants were collected and assayed for IL-12p70. Note that production of IL-12p70 occurred only in the presence of both JR.2 and LPS and was inhibited by mAb against IFN-γ and CD1c but not CD1a. The sensitivity of the assay was 0.3 ng/ml. These results are representative of three independent experiments using different DC donors.
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fig6: IL-12p70 production by DCs requires both CD1-restricted γ/δ T cells and LPS. Immature DCs were incubated for 24 h with the JR.2 γ/δ T cell clone, LPS (10 ng/ml), or both JR.2 and LPS in the presence of blocking mAbs against IFN-γ, CD1c, or CD1a. The culture supernatants were collected and assayed for IL-12p70. Note that production of IL-12p70 occurred only in the presence of both JR.2 and LPS and was inhibited by mAb against IFN-γ and CD1c but not CD1a. The sensitivity of the assay was 0.3 ng/ml. These results are representative of three independent experiments using different DC donors.

Mentions: Maturation of DCs by microbial products such as LPS has been proposed to lead to an “exhausted” DCs unable to produce bioactive IL-12p70 upon subsequent ligation of CD40 by antigen-specific naive CD4+ T cells. Increasing evidence suggests that signals derived from host T cells, including soluble factors such as IFN-γ as well as cell surface molecules such as CD40L, may provide crucial second signals to the maturing DCs that are required for the production of IL-12p70 (4). Therefore, we cultured immature DCs in the presence of low levels of LPS alone (10 ng/ml) or together with the CD1c-restricted γ/δ clone JR.2 and assayed supernatants by ELISA for production of IL-12p70. DCs cultured for 12 h in the presence of LPS or JR.2 alone failed to produce IL-12 (<30 pg/ml), whereas DCs cultured in the presence of both LPS and JR.2 (T:DC ratio = 1:10) produced significant amounts of IL-12 (18.4 ± 7.8 ng/ml). This effect could be partially inhibited by the addition of anti–IFN-γ mAb (∼63% inhibition) suggesting a role for this cytokine in the ability of these DCs to make bioactive IL-12. The addition of mAb against CD1c also efficiently blocked the production of IL-12 (∼87% inhibition) further supporting that recognition of CD1c expressed by the immature DCs by JR.2 γ/δ T cells was critical for the production of IL-12 (Fig. 6) .


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)

IL-12p70 production by DCs requires both CD1-restricted γ/δ T cells and LPS. Immature DCs were incubated for 24 h with the JR.2 γ/δ T cell clone, LPS (10 ng/ml), or both JR.2 and LPS in the presence of blocking mAbs against IFN-γ, CD1c, or CD1a. The culture supernatants were collected and assayed for IL-12p70. Note that production of IL-12p70 occurred only in the presence of both JR.2 and LPS and was inhibited by mAb against IFN-γ and CD1c but not CD1a. The sensitivity of the assay was 0.3 ng/ml. These results are representative of three independent experiments using different DC donors.
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Related In: Results  -  Collection

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fig6: IL-12p70 production by DCs requires both CD1-restricted γ/δ T cells and LPS. Immature DCs were incubated for 24 h with the JR.2 γ/δ T cell clone, LPS (10 ng/ml), or both JR.2 and LPS in the presence of blocking mAbs against IFN-γ, CD1c, or CD1a. The culture supernatants were collected and assayed for IL-12p70. Note that production of IL-12p70 occurred only in the presence of both JR.2 and LPS and was inhibited by mAb against IFN-γ and CD1c but not CD1a. The sensitivity of the assay was 0.3 ng/ml. These results are representative of three independent experiments using different DC donors.
Mentions: Maturation of DCs by microbial products such as LPS has been proposed to lead to an “exhausted” DCs unable to produce bioactive IL-12p70 upon subsequent ligation of CD40 by antigen-specific naive CD4+ T cells. Increasing evidence suggests that signals derived from host T cells, including soluble factors such as IFN-γ as well as cell surface molecules such as CD40L, may provide crucial second signals to the maturing DCs that are required for the production of IL-12p70 (4). Therefore, we cultured immature DCs in the presence of low levels of LPS alone (10 ng/ml) or together with the CD1c-restricted γ/δ clone JR.2 and assayed supernatants by ELISA for production of IL-12p70. DCs cultured for 12 h in the presence of LPS or JR.2 alone failed to produce IL-12 (<30 pg/ml), whereas DCs cultured in the presence of both LPS and JR.2 (T:DC ratio = 1:10) produced significant amounts of IL-12 (18.4 ± 7.8 ng/ml). This effect could be partially inhibited by the addition of anti–IFN-γ mAb (∼63% inhibition) suggesting a role for this cytokine in the ability of these DCs to make bioactive IL-12. The addition of mAb against CD1c also efficiently blocked the production of IL-12 (∼87% inhibition) further supporting that recognition of CD1c expressed by the immature DCs by JR.2 γ/δ T cells was critical for the production of IL-12 (Fig. 6) .

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