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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
| Content Provider | Scilit |
|---|---|
| Author | Yu, Qigui Kovacs, Colin Yue, Feng Yun Ostrowski, Mario A. |
| Copyright Year | 2004 |
| Description | 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. |
| Ending Page | 6056 |
| Page Count | 10 |
| Starting Page | 6047 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.172.10.6047 |
| Journal | The Journal of Immunology |
| Issue Number | 10 |
| Volume Number | 172 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2004-05-15 |
| Access Restriction | Open |
| Subject Keyword | Extracellular Signal Signal Regulated Regulated Kinase |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
