title: Lung dendritic cells are stimulated by ultrafine particles and play a key role in particle adjuvant activity.
abstract: BACKGROUND
  The adjuvant activity of air pollution particles on allergic airway sensitization is well known, but the cellular mechanisms underlying this adjuvant potential are not clear.
  
  
  OBJECTIVE
  We sough to study the role of dendritic cells and the costimulatory molecules CD80 and CD86 in the adjuvant activity of ultrafine carbon black particles (CBP).
  
  
  METHODS
  The proliferation of CFSE-labeled DO11.10 CD4 cells was studied after intranasal exposure to particles and ovalbumin (OVA). Next the frequency of myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells and their expression of CD80 and CD86 were studied in the peribronchial lymph nodes (PBLNs). The expression of costimulatory molecules was also studied on bone marrow-derived mDCs after exposure to CBPs in vitro, and the importance of costimulation in CBP adjuvant activity was assessed by using CD80/CD86-deficient mice or cytotoxic T lymphocyte-associated antigen 4 (CTLA4)-Ig in vivo.
  
  
  RESULTS
  Our data show that CBPs plus OVA caused proliferation of DO11.10 CD4 cells and high levels of cytokine production in the PBLNs. Furthermore, the combined CBP plus OVA exposure increased the number of mDCs and expression of costimulatory molecules in the PBLNs. In addition, CBPs upregulated the expression of CD80/CD86 molecules on dendritic cells in vitro, which are necessary for the particle adjuvant effects in vivo.
  
  
  CONCLUSIONS
  Together this study shows the importance of dendritic cells and costimulation in particle adjuvant activity. Furthermore, we show for the first time that CBPs can also directly induce maturation of dendritic cells.
authors.affiliation: Department of Immunotoxicology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands. c.dehaar@erasmusmc.nl
authors.forename: Colin
authors.initials: C
authors.lastname: de Haar
authors.forename: Mirjam
authors.initials: M
authors.lastname: Kool
authors.forename: Ine
authors.initials: I
authors.lastname: Hassing
authors.forename: Marianne
authors.initials: M
authors.lastname: Bol
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
authors.forename: Raymond
authors.initials: R
authors.lastname: Pieters
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D019264:Adoptive Transfer; D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005452:Fluoresceins; D008168:Lung / Q000166:cytology / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D010316:Particle Size; D052638:Particulate Matter / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000276:immunology; D053260:Soot / Q000494:pharmacology*; D013388:Succinimides
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D000276:Adjuvants, Immunologic; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016207:Cytokines; D005452:Fluoresceins; D052638:Particulate Matter; D053260:Soot; D013388:Succinimides; D010047:Ovalbumin