title: Depletion of natural CD4+CD25+ T regulatory cells with anti-CD25 antibody does not change the course of Pseudomonas aeruginosa-induced acute lung infection in mice.
abstract: Pseudomonas aeruginosa is a common cause of lung infection in immune compromised individuals. Studies in humans and mice have demonstrated that P. aeruginosa lung infection is associated with a predominant Th2 immune response, whereas Th1 responses are accompanied by a better pulmonary outcome. Regulatory T cells (Tregs) are a subpopulation of T cells with unique immunologic characteristics that suppress effector T cell functions. Whether Tregs contribute to P. aeruginosa-induced host responses has not been studied previously. We found that P. aeruginosa lung infection induced an increase in natural Treg cells (CD4+CD25+FOXP3+ T cells) in the spleen of mice. To investigate a role of natural CD4+CD25+ Tregs in the host response to P. aeruginosa lung infection in vivo, anti-CD25 Ab was used to deplete endogenous CD4+CD25+ Tregs. Anti-CD25 treatment depleted 90% of CD4+CD25+FOXP3+ cells. Surprisingly, no differences of P. aeruginosa-induced NF-kappaB activation and cytokine/chemokine production (IL-1beta, TNF, IL-6, IL-10, RANTES or MIP-2) were observed between anti-CD25-treated and isotype control Ab-treated animals. Similarly, no differences in lung histology and airway neutrophil infiltration were observed between anti-CD25 and control Ab-treated animals. Furthermore, no difference in survival outcome was found between anti-CD25 and control Ab-treated animals. These data demonstrate that although P. aeruginosa lung infection causes an increase of Tregs, the endogenous natural CD4+CD25+ Treg cells do not contribute significantly to the host response to this bacterium.
authors.affiliation: Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
authors.forename: Svetlana O
authors.initials: SO
authors.lastname: Carrigan
authors.forename: Yong Jun
authors.initials: YJ
authors.lastname: Yang
authors.forename: Thomas
authors.initials: T
authors.lastname: Issekutz
authors.forename: Nicholas
authors.initials: N
authors.lastname: Forward
authors.forename: David
authors.initials: D
authors.lastname: Hoskin
authors.forename: Brent
authors.initials: B
authors.lastname: Johnston
authors.forename: Tong-Jun
authors.initials: TJ
authors.lastname: Lin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D016207:Cytokines / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018375:Neutrophil Activation; D009504:Neutrophils / Q000473:pathology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D016328:NF-kappa B