title: Identification of a human CD8+ regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4.
abstract: Regulatory T cells (Treg) comprise multiple subsets and are important in controlling immunity and inflammation. However, the induction and mode of action of the various distinct Treg subsets remain ill defined, particularly in humans. Here, we describe a human CD8+ lymphocyte activation gene-3 (LAG-3)+CD25+FoxP3+ Treg subset, which suppresses T cells partly through the secretion of CC chemokine ligand 4 (CCL4), which can inhibit T cell activation by interfering with T cell receptor signaling. CD8+ Tregs are expanded by antigen in in vivo-primed donors, and can be detected in pathogen-infected human tissue. This CD8+LAG-3+CD25+FoxP3+CCL4+ Treg subset thus may play a role in immunoregulation in humans, including infectious diseases.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
authors.forename: Simone A
authors.initials: SA
authors.lastname: Joosten
authors.forename: Krista E
authors.initials: KE
authors.lastname: van Meijgaarden
authors.forename: Nigel D L
authors.initials: ND
authors.lastname: Savage
authors.forename: Tjitske
authors.initials: T
authors.lastname: de Boer
authors.forename: Frédéric
authors.initials: F
authors.lastname: Triebel
authors.forename: Annemieke
authors.initials: A
authors.lastname: van der Wal
authors.forename: Emile
authors.initials: E
authors.lastname: de Heer
authors.forename: Michèl R
authors.initials: MR
authors.lastname: Klein
authors.forename: Annemieke
authors.initials: A
authors.lastname: Geluk
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000032:analysis / Q000502:physiology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006099:Granuloma / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; C066507:CCL4 protein, human; D016827:CD8 Antigens; D054407:Chemokine CCL4; D019742:Chemokines, CC; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D002118:Calcium; D000093322:Lymphocyte Activation Gene 3 Protein