Modulation of antigen-specific T and B cell responses influence bacterial clearance of non-typeable Haemophilus influenzae from the lung in a rat model

Abstract

This study investigates antigen-specific B and T cell responses following mucosal immunization with the major outer membrane protein, P2, from non-typeable Haemophilus influenzae (NTHi) and the role of these responses in bacterial clearance following pulmonary challenge. Modification of the immunization preparation by the inclusion of sodium dodecyl sulphate (SDS) with the adjuvant, incomplete Freund's, differentially affects the T and B cell responses to the P2 antigen. Rats received an intra-Peyer's patch-immunization with P2 with or without the inclusion of 1% (w/v) SDS, were boosted via an intratracheal administration of P2 alone on day 14, and challenged with live NTHi in the lungs on day 21. There were significant differences in the rate of bacterial clearance between the different P2-immunized groups and the non-immune group. The inclusion of SDS with P2 resulted in enhanced bacterial clearance. This clearance corresponded to an enhancement of P2-specific lymphocyte proliferation by CD4+ T helper cells but a decrease (reduced ≈ 75%) in anti-P2 IgG and IgA in both serum and bronchoalveolar lavage washings. P2-specific IgM levels were not altered. IgG subclass analysis indicated that the inclusion of SDS had caused a significant reduction in IgG 2a and an increase in IgG 1. The data indicates that the magnitude of antibody levels to P2 may not be as important as T cell responses in enhancing clearance of NTHi in the lung, in vivo, and that immunization targeting enhancement of antigen-specific T cells may be important to inclucing effective immunity to NTHi.