title: Foxp3⁺ regulatory T cells exert asymmetric control over murine helper responses by inducing Th2 cell apoptosis.
abstract: Foxp3(+) regulatory T cells play a pivotal role in maintaining self-tolerance and immune homeostasis. In the absence of regulatory T cells, generalized immune activation and multiorgan T cell-driven pathology occurs. Although the phenomenon of immunologic control by Foxp3(+) regulatory T cells is well recognized, the comparative effect over different arms of the immune system has not been thoroughly investigated. Here, we generated a cohort of mice with a continuum of regulatory T-cell frequencies ranging from physiologic levels to complete deficiency. This titration of regulatory T-cell depletion was used to determine how different effector subsets are controlled. We found that in vivo Foxp3(+) regulatory T-cell frequency had a proportionate relationship with generalized T-cell activation and Th1 magnitude, but it had a surprising disproportionate relationship with Th2 magnitude. The asymmetric regulation was associated with efficient suppression of Th2 cells through additional regulations on the apoptosis rate in Th2 cells and not Th1 cells and could be replicated by CTLA4-Ig or anti-IL-2 Ab. These results indicate that the Th2 arm of the immune system is under tighter control by regulatory T cells than the Th1 arm, suggesting that Th2-driven diseases may be more responsive to regulatory T-cell manipulation.
authors.affiliation: VIB, Leuven, Belgium.
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
authors.forename: John A
authors.initials: JA
authors.lastname: Altin
authors.forename: Lydia E
authors.initials: LE
authors.lastname: Makaroff
authors.forename: Dean
authors.initials: D
authors.lastname: Franckaert
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Cook
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Goodnow
authors.forename: James
authors.initials: J
authors.lastname: Dooley
authors.forename: Adrian
authors.initials: A
authors.lastname: Liston
mesh_terms: D000069594:Abatacept; D000818:Animals; D017209:Apoptosis; D051858:Forkhead Transcription Factors / Q000276:immunology*; D018796:Immunoconjugates / Q000276:immunology; D007166:Immunosuppressive Agents / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D000069594:Abatacept