Blood Myeloid Dendritic Cells from HIV-1-Infected Individuals Display a Proapoptotic Profile Characterized by Decreased Bcl-2 Levels and by Caspase-3+ Frequencies That Are Associated with Levels of Plasma Viremia and T Cell Activation in an Exploratory Study

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.

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Human CD14hi monocytes and myeloid dendritic cells provide a cell contact–dependent costimulatory signal for early CD40 ligand expression

Blood ◽

10.1182/blood-2008-01-130252 ◽

2011 ◽

Vol 117 (5) ◽

pp. 1585-1594 ◽

Cited By ~ 5

Author(s):

Sagarika Chakrabarty ◽

James T. Snyder ◽

Jijia Shen ◽

Hooman Azmi ◽

Paul Q. Hu ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

T Cell ◽

B Cell ◽

T Cell Activation ◽

Cell Activation ◽

Myeloid Dendritic Cells ◽

A Cell ◽

Cd40l Expression ◽

Antigen Presenting

Abstract CD40L on CD4+ T cells plays a vital role in the activation of antigen-presenting cells, thus catalyzing a positive feedback loop for T-cell activation. Despite the pivotal juxtaposition of CD40L between antigen-presenting cells and T-cell activation, only a T-cell receptor stimulus is thought to be required for early CD40L surface expression. We show, for the first time, that CD40L expression on peripheral blood CD4+ T cells is highly dependent on a cell-cell interaction with CD14hiCD16− monocytes. Interactions with ICAM-1, LFA-3, and to a lesser extent CD80/CD86 contribute to this enhancement of CD40L expression but are not themselves sufficient. The contact-mediated increase in CD40L expression is dependent on new mRNA and protein synthesis. Circulating myeloid dendritic cells also possess this costimulatory activity. By contrast, CD14loCD16+ monocytes, plasmacytoid dendritic cells, B-cell lymphoma lines, and resting, activated, and Epstein-Barr virus–immortalized primary B cells all lack the capacity to up-regulate early CD40L. The latter indicates that a human B cell cannot activate its cognate T cell to deliver CD40L-mediated help. This finding has functional implications for the role of biphasic CD40L expression, suggesting that the early phase is associated with antigen-presenting cell activation, whereas the late phase is related to B-cell activation.

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Faculty Opinions recommendation of HIV-1 capture and antigen presentation by dendritic cells: enhanced viral capture does not correlate with better T cell activation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717248057.792503006 ◽

2012 ◽

Author(s):

Yufei Wang ◽

Karolin Hijazi

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Antigen Presentation ◽

T Cell Activation ◽

Cell Activation ◽

Hiv 1

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

Blood ◽

10.1182/blood.v96.5.1865 ◽

2000 ◽

Vol 96 (5) ◽

pp. 1865-1872 ◽

Cited By ~ 78

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.

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HIV-1 capture and antigen presentation by dendritic cells: enhanced viral capture does not correlate with better T-Cell activation

Retrovirology ◽

10.1186/1742-4690-9-s2-p2 ◽

2012 ◽

Vol 9 (S2) ◽

Cited By ~ 1

Author(s):

M Rodriguez-Plata ◽

A Urrutia ◽

S Cardinaud ◽

M Buzon ◽

N Izquierdo-Useros ◽

...

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Antigen Presentation ◽

T Cell Activation ◽

Cell Activation ◽

Hiv 1

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The Efficacy of Abatacept in Reducing Synovial T Cell Activation by CD1c Myeloid Dendritic Cells Is Overruled by the Stimulatory Effects of T Cell-Activating Cytokines

Arthritis & Rheumatology ◽

10.1002/art.38982 ◽

2015 ◽

Vol 67 (3) ◽

pp. 637-644 ◽

Cited By ~ 8

Author(s):

F. M. Moret ◽

J. W. J. Bijlsma ◽

F. P. J. G. Lafeber ◽

J. A. G. van Roon

Keyword(s):

Dendritic Cells ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Myeloid Dendritic Cells

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

Journal of Experimental Medicine ◽

10.1084/jem.189.3.593 ◽

1999 ◽

Vol 189 (3) ◽

pp. 593-598 ◽

Cited By ~ 128

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.

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