title: Human CD4+ T cells express TLR5 and its ligand flagellin enhances the suppressive capacity and expression of FOXP3 in CD4+CD25+ T regulatory cells.
abstract: Germline encoded pattern recognition receptors, such as TLRs, provide a critical link between the innate and adaptive immune systems. There is also evidence to suggest that pathogen-associated molecular patterns may have the capacity to modulate immune responses via direct effects on CD4+ T cells. Given the key role of both CD4+CD25+ T regulatory (Treg) cells and the TLR5 ligand flagellin in regulating mucosal immune responses, we investigated whether TLR5 may directly influence T cell function. We found that both human CD4+CD25+ Treg and CD4+CD25- T cells express TLR5 at levels comparable to those on monocytes and dendritic cells. Costimulation of effector T cells with anti-CD3 and flagellin resulted in enhanced proliferation and production of IL-2, at levels equivalent to those achieved by costimulation with CD28. In contrast, costimulation with flagellin did not break the hyporesponsiveness of CD4+CD25+ Treg cells, but rather, potently increased their suppressive capacity and enhanced expression of FOXP3. These observations suggest that, in addition to their APC-mediated indirect effects, TLR ligands have the capacity to directly regulate T cell responses and modulate the suppressive activity of Treg cells.
authors.affiliation: Department of Surgery, University of British Columbia and Immunity and Infection Centre, Vancouver, BC.
authors.forename: Natasha K
authors.initials: NK
authors.lastname: Crellin
authors.forename: Rosa V
authors.initials: RV
authors.lastname: Garcia
authors.forename: Omeed
authors.initials: O
authors.lastname: Hadisfar
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Allan
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Steiner
authors.forename: Megan K
authors.initials: MK
authors.lastname: Levings
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D005408:Flagellin / Q000494:pharmacology*; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D015375:Receptors, Interleukin-2; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D051198:Toll-Like Receptor 5 / Q000032:analysis / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D005408:Flagellin