title: Increased natural CD4+CD25+ regulatory T cells and their suppressor activity do not contribute to mortality in murine polymicrobial sepsis.
abstract: Regulatory T cells (Tregs), including natural CD4+CD25+ Tregs and inducible IL-10 producing T regulatory type 1 (T(R)1) cells, maintain tolerance and inhibit autoimmunity. Recently, increased percentages of Tregs have been observed in the blood of septic patients, and ex vivo-activated Tregs were shown to prevent polymicrobial sepsis mortality. Whether endogenous Tregs contribute to sepsis outcome remains unclear. Polymicrobial sepsis, induced by cecal ligation and puncture, caused an increased number of splenic Tregs compared with sham-treated mice. Splenic CD4+CD25+ T cells from septic mice expressed higher levels of Foxp3 mRNA and were more efficient suppressors of CD4+CD25- T effector cell proliferation. Isolated CD4+ T cells from septic mice displayed increased intracellular IL-10 staining following stimulation, indicating that T(R)1 cells may also be elevated in sepsis. Surprisingly, Ab depletion of total CD4+ or CD4+CD25+ populations did not affect mortality. Furthermore, no difference in survival outcome was found between CD25 or IL-10 null mice and wild-type littermates, indicating that Treg or T(R)1-generated IL-10 are not required for survival. These results demonstrate that, although sepsis causes a relative increase in Treg number and increases their suppressive function, their presence does not contribute significantly to overall survival in this model.
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Philip O
authors.initials: PO
authors.lastname: Scumpia
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Delano
authors.forename: Kindra M
authors.initials: KM
authors.lastname: Kelly
authors.forename: Kerri A
authors.initials: KA
authors.lastname: O'Malley
authors.forename: Philip A
authors.initials: PA
authors.lastname: Efron
authors.forename: Priscilla F
authors.initials: PF
authors.lastname: McAuliffe
authors.forename: Todd
authors.initials: T
authors.lastname: Brusko
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ungaro
authors.forename: Tolga
authors.initials: T
authors.lastname: Barker
authors.forename: James L
authors.initials: JL
authors.lastname: Wynn
authors.forename: Mark A
authors.initials: MA
authors.lastname: Atkinson
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
authors.forename: Michael J Clare
authors.initials: MJ
authors.lastname: Salzler
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology / Q000401:mortality*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10