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Human CD14hi monocytes and myeloid dendritic cells provide a cell contact-dependent costimulatory signal for early CD40 ligand expression.
- Source :
-
Blood [Blood] 2011 Feb 03; Vol. 117 (5), pp. 1585-94. Date of Electronic Publication: 2010 Jul 15. - Publication Year :
- 2011
-
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 CD14(hi)CD16(-) 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, CD14(lo)CD16(+) 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.
- Subjects :
- Antigen-Presenting Cells
Blotting, Northern
Blotting, Western
CD4-Positive T-Lymphocytes
CD40 Ligand genetics
CD58 Antigens genetics
CD58 Antigens metabolism
Cell Communication
Cells, Cultured
Flow Cytometry
Humans
Intercellular Adhesion Molecule-1 genetics
Intercellular Adhesion Molecule-1 metabolism
Lymphocyte Activation
Monocytes cytology
RNA, Messenger genetics
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
CD40 Antigens metabolism
CD40 Ligand metabolism
Cell Adhesion
Dendritic Cells metabolism
Lipopolysaccharide Receptors metabolism
Monocytes metabolism
Myeloid Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 117
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 20634374
- Full Text :
- https://doi.org/10.1182/blood-2008-01-130252