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

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.