title: CD103+ pulmonary dendritic cells preferentially acquire and present apoptotic cell-associated antigen.
abstract: Cells undergoing programmed cell death (apoptosis) are removed in situ by macrophages and dendritic cells (DCs) through a specialized form of phagocytosis (efferocytosis). In the lung, there are two primary DC subsets with the potential to migrate to the local lymph nodes (LNs) and initiate adaptive immune responses. In this study, we show that only CD103(+) DCs were able to acquire and transport apoptotic cells to the draining LNs and cross present apoptotic cell-associated antigen to CD8 T cells. In contrast, both the CD11b(hi) and the CD103(+) DCs were able to ingest and traffic latex beads or soluble antigen. CD103(+) DCs selectively exhibited high expression of TLR3, and ligation of this receptor led to enhanced in vivo cytotoxic T cell responses to apoptotic cell-associated antigen. The selective role for CD103(+) DCs was confirmed in Batf3(-/-) mice, which lack this DC subtype. Our findings suggest that CD103(+) DCs are the DC subset in the lung that captures and presents apoptotic cell-associated antigen under homeostatic and inflammatory conditions and raise the possibility for more focused immunological targeting to CD8 T cell responses.
authors.affiliation: Integrated Department of Immunology, National Jewish Health, University of Colorado Denver, Denver, CO 80206, USA.
authors.forename: A Nicole
authors.initials: AN
authors.lastname: Desch
authors.forename: Gwendalyn J
authors.initials: GJ
authors.lastname: Randolph
authors.forename: Kenneth
authors.initials: K
authors.lastname: Murphy
authors.forename: Emmanuel L
authors.initials: EL
authors.lastname: Gautier
authors.forename: Ross M
authors.initials: RM
authors.lastname: Kedl
authors.forename: Mireille H
authors.initials: MH
authors.lastname: Lahoud
authors.forename: Irina
authors.initials: I
authors.lastname: Caminschi
authors.forename: Ken
authors.initials: K
authors.lastname: Shortman
authors.forename: Peter M
authors.initials: PM
authors.lastname: Henson
authors.forename: Claudia V
authors.initials: CV
authors.lastname: Jakubzick
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000235:genetics / Q000276:immunology; D015703:Antigens, CD; D017209:Apoptosis / Q000276:immunology*; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D039001:Integrin alpha Chains; D008168:Lung / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000941:Antigens; D015703:Antigens, CD; D050976:Basic-Leucine Zipper Transcription Factors; D039001:Integrin alpha Chains; D012097:Repressor Proteins; C533289:SNFT protein, mouse; C091367:alpha E integrins