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The role of the p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and phosphoinositide-3-OH kinase signal transduction pathways in CD40 ligand-induced dendritic cell activation and expansion of virus-specific CD8+ T cell memory responses.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2004 May 15; Vol. 172 (10), pp. 6047-56. - Publication Year :
- 2004
-
Abstract
- Mature dendritic cells (DCs) are central to the development of optimal T cell immune responses. CD40 ligand (CD40L, CD154) is one of the most potent maturation stimuli for immature DCs. We studied the role of three signaling pathways, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and phosphoinositide-3-OH kinase (PI3K), in CD40L-induced monocyte-derived DC activation, survival, and expansion of virus-specific CD8(+) T cell responses. p38 MAPK pathway was critical for CD40L-mediated up-regulation of CD83, a marker of DC maturation. CD40L-induced monocyte-derived DC IL-12 production was mediated by both the p38 MAPK and PI3K pathways. CD40L-mediated DC survival was mostly mediated by the PI3K pathway, with smaller contributions by p38 MAPK and ERK pathways. Finally, the p38 MAPK pathway was most important in mediating CD40L-stimulated DCs to induce strong allogeneic responses as well as expanding virus-specific memory CD8(+) T cell responses. Thus, although the p38 MAPK, PI3K, and ERK pathways independently affect various parameters of DC maturation induced by CD40L, the p38 MAPK pathway within CD40L-conditioned DCs is the most important pathway to maximally elicit T cell immune responses. This pathway should be exploited in vivo to either completely suppress or enhance CD8(+) T cell immune responses.
- Subjects :
- Cell Differentiation immunology
Cell Survival immunology
Coculture Techniques
Dendritic Cells cytology
Dendritic Cells enzymology
Down-Regulation immunology
Enzyme Inhibitors pharmacology
Epitopes, T-Lymphocyte immunology
Humans
Interleukin-12 antagonists & inhibitors
Interleukin-12 biosynthesis
Lymphocyte Activation immunology
Lymphocyte Culture Test, Mixed
Mitogen-Activated Protein Kinases antagonists & inhibitors
Mitogen-Activated Protein Kinases metabolism
Phosphatidylinositol 3-Kinases metabolism
Phosphoinositide-3 Kinase Inhibitors
Protein Serine-Threonine Kinases metabolism
Proto-Oncogene Proteins metabolism
Proto-Oncogene Proteins c-akt
p38 Mitogen-Activated Protein Kinases
CD40 Ligand pharmacology
Dendritic Cells immunology
HIV-1 immunology
Immunologic Memory
Mitogen-Activated Protein Kinases physiology
Phosphatidylinositol 3-Kinases physiology
Signal Transduction immunology
T-Lymphocytes, Cytotoxic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 172
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 15128788
- Full Text :
- https://doi.org/10.4049/jimmunol.172.10.6047