title: CD70 expression by dendritic cells plays a critical role in the immunogenicity of CD40-independent, CD4+ T cell-dependent, licensed CD8+ T cell responses.
abstract: The stimulation of DC by CD4(+) T cells is known to condition DC to activate naïve CD8(+) T cells, predominantly via CD40-CD40L interactions. It has been proposed that a critical consequence of DC conditioning is the induction of CD70 expression. Whether and how CD70 induction contributes to CD8(+) T cell responses in the absence of CD40-CD40L interactions are unknown. CD8(+) T cell responses to adenoviral- or DC-based immunization of CD40-deficient mice revealed a CD40-independent, CD4(+) T cell-dependent pathway for CD70 induction on conventional DC. This pathway and subsequent CD8(+) T cell responses were enhanced by, but not dependent on, concomitant activation of TLR and in part, used TRANCE and LIGHT/LTalphabeta stimulation. Blocking TRANCE and LIGHT/LTalphabeta during stimulation reduced the immunogenicity of CD40-deficient DC. These data support the hypothesis that induction of CD70 expression on DC after an encounter with activated CD4(+) T cells is a major component of CD4(+) T cell-mediated licensing of DC. Further, multiple pathways exist for CD4(+) T cells to elicit CD70 expression on DC. These data in part explain the capacity of CD40-deficient mice to mount CD8(+) T cell responses and may provide additional targets for immunotherapy in situations when CD40-mediated licensing is compromised.
authors: Department of Pathology, Human Immune Therapy Center, University of Virginia Health System, Carter-Harrison MR6, Room G526, 345 Crispell Dr., Charlottesville, VA 22908, USA.
authors: Katherine E
authors: KE
authors: Van Deusen
authors: Rohan
authors: R
authors: Rajapakse
authors: Timothy N J
authors: TN
authors: Bullock
mesh_terms: D000257:Adenoviridae Infections / Q000276:immunology; D000818:Animals; D053282:CD27 Ligand / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D002450:Cell Communication / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D053361:Lymphotoxin alpha1, beta2 Heterotrimer / Q000378:metabolism; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D053245:RANK Ligand / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D053282:CD27 Ligand; D019013:CD40 Antigens; D053361:Lymphotoxin alpha1, beta2 Heterotrimer; D053594:Myeloid Differentiation Factor 88; D010455:Peptides; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D051193:Toll-Like Receptors; D023201:CD40 Ligand