Identification of a human CD8+ regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4.
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.
Joosten
Simone A
SA
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.
van Meijgaarden
Krista E
KE
Savage
Nigel D L
ND
de Boer
Tjitske
T
Triebel
Frédéric
F
van der Wal
Annemieke
A
de Heer
Emile
E
Klein
Michèl R
MR
Geluk
Annemieke
A
Ottenhoff
Tom H M
TH
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
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