title: Foxp3+ regulatory T cells impede the priming of protective CD8+ T cells.
abstract: T cell activation is controlled by incompletely defined opposing stimulation and suppression signals that together sustain the balance between optimal host defense against infection and peripheral tolerance. In this article, we explore the impacts of Foxp3(+) regulatory T cell (Treg) suppression in priming Ag-specific T cell activation under conditions of noninfection and infection. We find the transient ablation of Foxp3(+) Tregs unleashes the robust expansion and activation of peptide-stimulated CD8(+) T cells that provide protection against Listeria monocytogenes infection in an Ag-specific fashion. By contrast, Treg ablation had nonsignificant impacts on the CD8(+) T cell response primed by infection with recombinant L. monocytogenes. Similarly, nonrecombinant L. monocytogenes administered with peptide stimulated the expansion and activation of CD8(+) T cells that paralleled the response primed by Treg ablation. Interestingly, these adjuvant properties of L. monocytogenes did not require CD8(+) T cell stimulation by IL-12 produced in response to infection, but instead were associated with sharp reductions in Foxp3(+) Treg suppressive potency. Therefore, Foxp3(+) Tregs impose critical barriers that, when overcome naturally during infection or artificially with ablation, allow the priming of protective Ag-specific CD8(+) T cells.
authors.affiliation: Department of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN 55455, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Ertelt
authors.forename: Jared H
authors.initials: JH
authors.lastname: Rowe
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Mysz
authors.forename: Charanjeet
authors.initials: C
authors.lastname: Singh
authors.forename: Monika
authors.initials: M
authors.lastname: Roychowdhury
authors.forename: Marijo N
authors.initials: MN
authors.lastname: Aguilera
authors.forename: Sing Sing
authors.initials: SS
authors.lastname: Way
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse