title: Regulation of TB vaccine-induced airway luminal T cells by respiratory exposure to endotoxin.
abstract: Tuberculosis (TB) vaccine-induced airway luminal T cells (ALT) have recently been shown to be critical to host defense against pulmonary TB. However, the mechanisms that maintain memory ALT remain poorly understood. In particular, whether respiratory mucosal exposure to environmental agents such as endotoxin may regulate the size of vaccine-induced ALT population is still unclear. Using a murine model of respiratory genetic TB vaccination and respiratory LPS exposure, we have addressed this issue in the current study. We have found that single or repeated LPS exposure increases the number of antigen-specific ALT which are capable of robust secondary responses to pulmonary mycobacterial challenge. To investigate the potential mechanisms by which LPS exposure modulates the ALT population, we have examined the role of ALT proliferation and peripheral T cell recruitment. We have found that LPS exposure-increased ALT is not dependent on increased ALT proliferation as respiratory LPS exposure does not significantly increase the rate of proliferation of ALT. But rather, we find it to be dependent upon the recruitment of peripheral T cells into the airway lumen as blockade of peripheral T cell supplies markedly reduces the initially increased ALT. Thus, our data suggest that environmental exposure to airborne agents such as endotoxin has a profound modulatory effect on TB vaccine-elicited T cells within the respiratory tract. Our study provides a new, M.tb antigen-independent mechanism by which the respiratory mucosal anti-TB memory T cells may be maintained.
authors: McMaster Immunology Research Centre, and Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Xuerong
authors: X
authors: Chen
authors: Fangming
authors: F
authors: Xiu
authors: Carly N
authors: CN
authors: Horvath
authors: Daniela
authors: D
authors: Damjanovic
authors: Niroshan
authors: N
authors: Thanthrige-Don
authors: Mangalakumari
authors: M
authors: Jeyanathan
authors: Zhou
authors: Z
authors: Xing
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000382:microbiology; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000517:prevention & control
chemical_list: D000942:Antigens, Bacterial; D018925:Chemokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D032581:Tuberculosis Vaccines