title: Removal of regulatory T cells prevents secondary chronic infection but increases the mortality of subsequent sub-acute infection in sepsis mice.
abstract: The immunosuppression following initial septic insult impairs resistance to secondary infection. Modulation of lymphocytes population may help to develop an effective therapeutic strategy. In this study, lipopolysaccharide (LPS)-induced endotoxemia was employed as the initial septic insult. 24 hours later, mice underwent cecal ligation and puncture to induce chronic or sub-acute peritonitis. Potential usefulness of T regs deletion antibody (anti-CD25) in improving LPS-induced immunosuppression and the survival of subsequent different infections were evaluated. LPS injection induced lymphocyte loss and led to decreased IL-6, TNF-α and IFN-γ, and weakened bacteria clearance upon chronic peritonitis at 24 h post-LPS, whereas reconstitution with lymphocytes reversed these changes. LPS-induced T regs expansion contributed to T and NK cells decrease in number and activity during sepsis. Depletion of T regs using anti-CD25 antibodies partly prevented lymphocyte loss and increased the responses of T and NK cells to subsequent stimulation, resulting in significantly increased bacterial clearance and survival in a 2-hit model of chronic peritonitis, but which significantly increased early mortality upon subsequently sub-acute infection. Yet, using lower dosage of anti-CD25 antibodies to moderate down-regulate T regs levels could partly improve bacterial clearance and survival in either chronic or sub-acute infection. These results demonstrate that using anti-CD25 antibodies to deplete T regs can ameliorate immunosuppression through increasing T cells and NK cells responses in sepsis, which is beneficial for preventing subsequently chronic infection, but will probably bring some deleterious effects for subsequent sub-acute infection.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Ruichao
authors.initials: R
authors.lastname: Huo
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Xiaoya
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Chang
authors.affiliation: Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO, United States of America.
authors.forename: Shan-Lu
authors.initials: SL
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Dewen
authors.initials: D
authors.lastname: Tong
authors.affiliation: Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D002908:Chronic Disease; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D018805:Sepsis / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D008070:Lipopolysaccharides
keywords: Immune response; Immunity; Immunology and Microbiology Section; immunosuppression; immunotherapeutic approach; lymphocyte; secondary infection; sepsis