title: Differential roles of IL-16 and CD28/B7 costimulation in the generation of T-lymphocyte chemotactic activity in the bronchial mucosa of mild and moderate asthmatic individuals.
abstract: BACKGROUND
  IL-16 is an important T-cell chemotactic cytokine in asthmatic airways; its release from allergen-stimulated bronchial mucosa in mild asthma has been shown to be dependent on CD28/B7 costimulation.
  
  
  OBJECTIVE
  We have extended our previous studies to investigate the role of IL-16 and CD28/B7 costimulation in T-lymphocyte chemotactic activity (TLCA) released from the bronchial mucosa in more severe asthma.
  
  
  METHODS
  TLCA was determined in the supernatants of induced sputum and allergen-stimulated bronchial mucosal explants from healthy volunteers and volunteers with mild and moderately severe asthma by means of a Boyden chamber technique. The contribution of IL-16 to the activity was evaluated through use of a neutralizing monoclonal antibody; the contribution of CD28/B7 costimulation to allergen-induced release of TLCA was determined through use of CTLA4-Ig fusion protein and neutralizing monoclonal antibodies to CD80 (B7.1) and CD86 (B7.2).
  
  
  RESULTS
  Induced sputum and unstimulated explants from asthmatic subjects generated significant spontaneous TLCA (P <.05). Both mild and moderate asthmatic explants showed significantly elevated Dermatophagoides pteronyssinus -induced release of TLCA, but only in mild asthma could sputum and allergen-stimulated explant TLCA be inhibited by anti-IL-16 (median inhibition, 39% and 59%; P <.05). In addition, allergen released significant quantities of IL-16 from mild asthmatic explants (P <.05) but not from moderate asthmatic explants. Antibodies to the CD28 counter-ligands CD80 and CD86 inhibited allergen-induced release of TLCA in mild asthmatic explants by 94% (P <.05) and 62%, but TLCA release from moderate asthmatic explants was unaffected by CTLA4-Ig.
  
  
  CONCLUSIONS
  These results show that TLCA release in moderate asthmatic airways, in contrast to mild asthmatic airways, is not dependent on CD28/B7 costimulation and does not involve IL-16.
authors.affiliation: Respiratory Cell & Molecular Biology Section, Division of Infection Inflammation & Repair, University of Southampton School of Medicine, United Kingdom.
authors.forename: Gordon
authors.initials: G
authors.lastname: Dent
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Hosking
authors.forename: James L
authors.initials: JL
authors.lastname: Lordan
authors.forename: Mark D
authors.initials: MD
authors.lastname: Steel
authors.forename: William W
authors.initials: WW
authors.lastname: Cruikshank
authors.forename: David M
authors.initials: DM
authors.lastname: Center
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Ellis
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Holgate
authors.forename: Donna E
authors.initials: DE
authors.lastname: Davies
authors.forename: Ratko
authors.initials: R
authors.lastname: Djukanović
mesh_terms: D000069594:Abatacept; D000328:Adult; D015703:Antigens, CD / Q000502:physiology; D000943:Antigens, Differentiation / Q000502:physiology; D001249:Asthma / Q000276:immunology*; D018122:B7-1 Antigen / Q000502:physiology*; D051940:B7-2 Antigen; D001980:Bronchi / Q000276:immunology*; D018106:CD28 Antigens / Q000502:physiology*; D060908:CTLA-4 Antigen; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005260:Female; D006801:Humans; D018796:Immunoconjugates; D019410:Interleukin-16 / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D008875:Middle Aged; D013183:Sputum / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D019410:Interleukin-16; D008562:Membrane Glycoproteins; D000069594:Abatacept