title: Tissue-expressed B7x affects the immune response to and outcome of lethal pulmonary infection.
abstract: B7x (B7-H4 or B7S1), a member of the B7 family, inhibits in vitro T cell proliferation and cytokine production by binding to an unidentified receptor on activated T cells, but its in vivo function remains largely unclear. We show that B7x protein was expressed in epithelial cells of the lung, but not in lymphoid tissues. To investigate the role of B7x in the lung, we determined the susceptibility of B7x-deficient (B7x(-/-)) mice to a lethal pulmonary infection with Streptococcus pneumoniae. B7x(-/-), but not B7-H3-deficient, mice were significantly more resistant to S. pneumoniae pulmonary infection than their wild-type (Wt) counterparts. B7x(-/-) mice had significantly lower bacterial burdens and levels of inflammatory cytokines in lungs as early as 12 h postinfection. They also had milder immunopathology that was localized in alveolar spaces, whereas Wt mice had severe inflammation that was perivascular. Control of infection in B7x(-/-) mice was associated with a marked increase in activated CD4 and CD8 T cells and fewer neutrophils in lungs, whereas the susceptible Wt mice had the opposite cellular profile. In B7x(-/-)Rag1(-/-) mice that lack T cells, reduction in bacterial burden was no longer observed. Control of S. pneumoniae and the increased survival observed was specific to the lung, because systemically infected B7x(-/-) mice were not resistant to infection. These data indicate that lung-expressed B7x negatively regulates T cells, and that in its absence, in B7x(-/-) mice, an enhanced T cell response contributed to reduced lethality in a pulmonary infection model with S. pneumoniae.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Hofmeyer
authors.forename: Lisa
authors.initials: L
authors.lastname: Scandiuzzi
authors.forename: Kaya
authors.initials: K
authors.lastname: Ghosh
authors.forename: Liise-Anne
authors.initials: LA
authors.lastname: Pirofski
authors.forename: Xingxing
authors.initials: X
authors.lastname: Zang
mesh_terms: D000818:Animals; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008221:Lymphoid Tissue / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017063:Outcome Assessment, Health Care; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D014018:Tissue Distribution / Q000235:genetics / Q000276:immunology; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1