Differentiation of myeloid dendritic cells into CD8α-positive dendritic cells in vivo

Blood ◽  
2000 ◽  
Vol 96 (5) ◽  
pp. 1865-1872 ◽  
Author(s):  
Miriam Merad ◽  
Lawrence Fong ◽  
Jakob Bogenberger ◽  
Edgar G. Engleman
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Wild Type Mouse ◽  
Interleukin 12 ◽  
Myeloid Dendritic Cells ◽  
Myeloid Antigens

Bone marrow-derived dendritic cells (DC) represent a family of antigen-presenting cells (APC) with varying phenotypes. For example, in mice, CD8α+ and CD8α− DC are thought to represent cells of lymphoid and myeloid origin, respectively. Langerhans cells (LC) of the epidermis are typical myeloid DC; they do not express CD8α, but they do express high levels of myeloid antigens such as CD11b and FcγR. By contrast, thymic DC, which derive from a lymphoid-related progenitor, express CD8α but only low levels of myeloid antigens. CD8α+ DC are also found in the spleen and lymph nodes (LN), but the origin of these cells has not been determined. By activating and labeling CD8α− epidermal LC in vivo, it was found that these cells expressed CD8α on migration to the draining LN. Similarly, CD8α− LC generated in vitro from a CD8 wild-type mouse and injected into the skin of a CD8αKO mouse expressed CD8α when they reached the draining LN. The results also show that CD8α+ LC are potent APC. After migration from skin, they localized in the T-cell areas of LN, secreted high levels of interleukin-12, interferon-γ, and chemokine-attracting T cells, and they induced antigen-specific T-cell activation. These results demonstrate that myeloid DC in the periphery can express CD8α when they migrate to the draining LN. CD8α expression on these DC appears to reflect a state of activation, mobilization, or both, rather than lineage.

Differentiation of myeloid dendritic cells into CD8α-positive dendritic cells in vivo

Blood ◽  
2000 ◽  
Vol 96 (5) ◽  
pp. 1865-1872 ◽  
Author(s):  
Miriam Merad ◽  
Lawrence Fong ◽  
Jakob Bogenberger ◽  
Edgar G. Engleman
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Wild Type Mouse ◽  
Interleukin 12 ◽  
Myeloid Dendritic Cells ◽  
Myeloid Antigens

Abstract Bone marrow-derived dendritic cells (DC) represent a family of antigen-presenting cells (APC) with varying phenotypes. For example, in mice, CD8α+ and CD8α− DC are thought to represent cells of lymphoid and myeloid origin, respectively. Langerhans cells (LC) of the epidermis are typical myeloid DC; they do not express CD8α, but they do express high levels of myeloid antigens such as CD11b and FcγR. By contrast, thymic DC, which derive from a lymphoid-related progenitor, express CD8α but only low levels of myeloid antigens. CD8α+ DC are also found in the spleen and lymph nodes (LN), but the origin of these cells has not been determined. By activating and labeling CD8α− epidermal LC in vivo, it was found that these cells expressed CD8α on migration to the draining LN. Similarly, CD8α− LC generated in vitro from a CD8 wild-type mouse and injected into the skin of a CD8αKO mouse expressed CD8α when they reached the draining LN. The results also show that CD8α+ LC are potent APC. After migration from skin, they localized in the T-cell areas of LN, secreted high levels of interleukin-12, interferon-γ, and chemokine-attracting T cells, and they induced antigen-specific T-cell activation. These results demonstrate that myeloid DC in the periphery can express CD8α when they migrate to the draining LN. CD8α expression on these DC appears to reflect a state of activation, mobilization, or both, rather than lineage.

scholarly journals Antigen-pulsed CD8α+ Dendritic Cells Generate an Immune Response after Subcutaneous Injection without Homing to the Draining Lymph Node

1999 ◽  
Vol 189 (3) ◽  
pp. 593-598 ◽  
Author(s):  
Adrian L. Smith ◽  
Barbara Fazekas de St. Groth
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Lymph Node ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Myeloid Dendritic Cells ◽  
Draining Lymph Node

Two subsets of murine splenic dendritic cells, derived from distinct precursors, can be distinguished by surface expression of CD8α homodimers. The functions of the two subsets remain controversial, although it has been suggested that the lymphoid-derived (CD8α+) subset induces tolerance, whereas the myeloid-derived (CD8α−) subset has been shown to prime naive T cells and to generate memory responses. To study their capacity to prime or tolerize naive CD4+ T cells in vivo, purified CD8α+ or CD8α− dendritic cells were injected subcutaneously into normal mice. In contrast to CD8α− dendritic cells, the CD8α+ fraction failed to traffic to the draining lymph node and did not generate responses to intravenous peptide. However, after in vitro pulsing with peptide, strong in vivo T cell responses to purified CD8α+ dendritic cells could be detected. Such responses may have been initiated via transfer of peptide–major histocompatibility complex complexes to migratory host CD8α− dendritic cells after injection. These data suggest that correlation of T helper cell type 1 (Th1) and Th2 priming with injection of CD8α+ and CD8α− dendritic cells, respectively, may not result from direct T cell activation by lymphoid versus myeloid dendritic cells, but rather from indirect modification of the response to immunogenic CD8α− dendritic cells by CD8α+ dendritic cells.

A subset of human monocyte-derived dendritic cells expresses high levels of interleukin-12 in response to combined CD40 ligand and interferon-γ treatment

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3499-3504 ◽  
Author(s):  
Paul J. Mosca ◽  
Amy C. Hobeika ◽  
Timothy M. Clay ◽  
Smita K. Nair ◽  
Elaine K. Thomas ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Human Monocyte ◽  
Cd40 Ligand ◽  
Cell Surface Expression ◽  
Interleukin 12 ◽  
Cytokine Detection

Abstract Dendritic cells (DCs) may arise from multiple lineages and progress through a series of intermediate stages until fully mature, at which time they are capable of optimal antigen presentation and T-cell activation. High cell surface expression of CD83 is presumed to correlate with full maturation of DCs, and a number of agents have been shown to increase CD83 expression on DCs. We hypothesized that interleukin 12 (IL-12) expression would be a more accurate marker of functionally mature DCs capable of activating antigen-specific T cells. We used combinations of signaling through CD40, using CD40 ligand trimer (CD40L), and interferon gamma to demonstrate that CD83 expression is necessary but not sufficient for optimal production of IL-12 by DCs. Phenotypically mature DCs could be induced to produce high levels of IL-12 p70 only when provided 2 simultaneous stimulatory signals. By intracellular cytokine detection, we determined that only a subset of cells that express high levels of CD80 and CD83 generate large amounts of IL-12. DCs matured with both signals are superior to DCs stimulated with the individual agents in activating antigen-specific T cell in vitro. These findings have important implications regarding the identification, characterization, and clinical application of functionally mature DCs.

scholarly journals Towards Identification of the Mechanisms of Action of Parasite-Derived Peptide GK1 on the Immunogenicity of an Influenza Vaccine

2009 ◽  
Vol 16 (9) ◽  
pp. 1338-1343 ◽  
Author(s):  
René Segura-Velázquez ◽  
Gladis Fragoso ◽  
Edda Sciutto ◽  
Adelaida Sarukhan
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Influenza Vaccine ◽  
T Cell Activation ◽  
Cell Activation ◽  
Mechanisms Of Action ◽  
The Body ◽  
Vaccine Adjuvants

ABSTRACT Previous studies have shown that the synthetic peptide GK1, derived from Taenia crassiceps cysticerci, enhances the immunogenicity of the commercial inactivated influenza vaccine Fluzone in both young and aged mice. In particular, antibody responses were much improved. Since GK1 is a peptide and is rapidly cleared from the body, it offers the possibility to improve vaccine performance without undesirable effects. This study was therefore designed to understand the mechanisms of action involved in the adjuvant properties of GK1. For this, transgenic mice expressing a T-cell receptor specific for an epitope from the influenza virus hemagglutinin (HA) protein were employed. The GK1 peptide significantly increased the in vivo proliferative response of HA-specific CD4+ T cells when it was coimmunized with the HA epitope. Dendritic cells treated in vitro with GK1 were capable of enhancing T-cell activation. Furthermore, in synergy with lipopolysaccharide, GK1 enhanced the expression of major histocompatibility complex class II and costimulatory molecules of dendritic cells and promoted the secretion of proinflammatory cytokines and chemokines upon antigen-driven T-cell interaction. These data provide important insights into the mechanism that underlies the GK1 adjuvant capacity observed previously and underline the feasibility of using the transgenic mouse model described herein as a tool for investigation of the modes of action of different influenza vaccine adjuvants.

Bone marrow microenvironment controls the in vivo differentiation of murine dendritic cells into osteoclasts

Blood ◽  
2008 ◽  
Vol 112 (13) ◽  
pp. 5074-5083 ◽  
Author(s):  
Abdelilah Wakkach ◽  
Anna Mansour ◽  
Romain Dacquin ◽  
Emmanuel Coste ◽  
Pierre Jurdic ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Bone Cells ◽  
Activated T Cells

Abstract Finding that activated T cells control osteoclast (OCL) differentiation has revealed the importance of the interactions between immune and bone cells. Dendritic cells (DCs) are responsible for T-cell activation and share common precursors with OCLs. Here we show that DCs participate in bone resorption more directly than simply through T-cell activation. We show that, among the splenic DC subsets, the conventional DCs have the higher osteoclastogenic potential in vitro. We demonstrate that conventional DCs differentiate into functional OCLs in vivo when injected into osteopetrotic oc/oc mice defective in OCL resorptive function. Moreover, this differentiation involves the presence of activated CD4+ T cells controlling a high RANK-L expression by bone marrow stromal cells. Our results open new insights in the differentiation of OCLs and DCs and offer new basis for analyzing the relations between bone and immune systems.

scholarly journals Deficiency of Bim in dendritic cells contributes to overactivation of lymphocytes and autoimmunity

Blood ◽  
2007 ◽  
Vol 109 (10) ◽  
pp. 4360-4367 ◽  
Author(s):  
Min Chen ◽  
Li Huang ◽  
Jin Wang
Keyword(s):  
Cell Death ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Autoantibody Production ◽  
Systemic Autoimmunity ◽  
Spontaneous Cell Death

Abstract Apoptosis in dendritic cells (DCs) can potentially regulate DC homeostasis and immune responses. We have previously observed that inhibition of the Fas signaling pathway in DCs results in spontaneous T-cell activation and the development of systemic autoimmunity in transgenic mice. However, the role for different apoptosis pathways in DCs in regulating DC homeostasis and immune tolerance remains to be determined. Bim, a BH3-only protein of the Bcl-2 family, was expressed at low levels in DCs and was significantly up-regulated by signaling from CD40 or toll-like receptors (TLRs). Because Bim−/− mice develop spontaneous systemic autoimmunity, we investigated whether Bim−/− DCs contributed to lymphoproliferation and autoimmunity in these mice. Bim−/− DCs showed decreased spontaneous cell death, and induced more robust T-cell activation in vitro and in vivo. Moreover, Bim−/− DCs induced autoantibody production after adoptive transfer. Our data suggest that Bim is important for regulating spontaneous cell death in DCs, and Bim-deficient DCs may contribute to the development of autoimmune diseases in Bim−/− mice.

A subset of human monocyte-derived dendritic cells expresses high levels of interleukin-12 in response to combined CD40 ligand and interferon-γ treatment

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3499-3504 ◽  
Author(s):  
Paul J. Mosca ◽  
Amy C. Hobeika ◽  
Timothy M. Clay ◽  
Smita K. Nair ◽  
Elaine K. Thomas ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Human Monocyte ◽  
Cd40 Ligand ◽  
Cell Surface Expression ◽  
Interleukin 12 ◽  
Cytokine Detection

Dendritic cells (DCs) may arise from multiple lineages and progress through a series of intermediate stages until fully mature, at which time they are capable of optimal antigen presentation and T-cell activation. High cell surface expression of CD83 is presumed to correlate with full maturation of DCs, and a number of agents have been shown to increase CD83 expression on DCs. We hypothesized that interleukin 12 (IL-12) expression would be a more accurate marker of functionally mature DCs capable of activating antigen-specific T cells. We used combinations of signaling through CD40, using CD40 ligand trimer (CD40L), and interferon gamma to demonstrate that CD83 expression is necessary but not sufficient for optimal production of IL-12 by DCs. Phenotypically mature DCs could be induced to produce high levels of IL-12 p70 only when provided 2 simultaneous stimulatory signals. By intracellular cytokine detection, we determined that only a subset of cells that express high levels of CD80 and CD83 generate large amounts of IL-12. DCs matured with both signals are superior to DCs stimulated with the individual agents in activating antigen-specific T cell in vitro. These findings have important implications regarding the identification, characterization, and clinical application of functionally mature DCs.

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