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.

CONCLUSION:

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: Gordon Dent, Lisa A Hosking, James L Lordan, Mark D Steel, William W Cruikshank, David M Center, Jonathan H Ellis, Stephen T Holgate, Donna E Davies, Ratko Djukanović
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 110 Issue 6 Pg. 906-14 (Dec 2002) ISSN: 0091-6749 [Print] United States
• PMID: 12464958 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Antigens, Differentiation
• B7-1 Antigen
• B7-2 Antigen
• CD28 Antigens
• CD86 protein, human
• CTLA-4 Antigen
• CTLA4 protein, human
• Immunoconjugates
• Interleukin-16
• Membrane Glycoproteins
• Abatacept

Topics

• Abatacept
• Adult
• Antigens, CD (physiology)
• Antigens, Differentiation (physiology)
• Asthma (immunology)
• B7-1 Antigen (physiology)
• B7-2 Antigen
• Bronchi (immunology)
• CD28 Antigens (physiology)
• CTLA-4 Antigen
• Chemotaxis, Leukocyte (immunology)
• Female
• Humans
• Immunoconjugates
• Interleukin-16 (physiology)
• Male
• Membrane Glycoproteins (physiology)
• Middle Aged
• Sputum (immunology)
• T-Lymphocytes (immunology)