CCR6 expression defines regulatory effector/memory-like cells within the CD25(+)CD4+ T-cell subset.
Regulatory CD25(+)CD4+ T cells (Treg cells) are a central element of peripheral tolerance. Little is known, however, about phenotypic and functional characteristics of these cells with regard to memory. In this study we show that the chemokine receptor CCR6 is expressed on a distinct subset of mouse Treg cells. Similar to their CD25- counterparts, CCR6+ Treg cells exhibit markers of activation, memory, and expansion that are indicative for an effector-memory function. They are memory-like cells, generated in vivo from CCR6(-)CD25+ T cells after the encounter of antigen. As conventional CD25- effector-memory T cells, they have a high turnover rate and, in contrast to CCR6- Treg cells, they respond rapidly to restimulation in vitro with up-regulation of interleukin 10. CCR6+ Treg cells are enriched in the peripheral blood and accumulate in the central nervous system after induction of experimental autoimmune encephalomyelitis (EAE). This subset therefore seems to represent a population of regulatory effector-memory T cells (T(REM)), destined to control potentially destructive immune responses directly in inflamed tissues. Importantly, these cells are also present in humans. Here the expression of CCR6 fully cosegregates with CD45RO, an established marker of human memory T cells.
Kleinewietfeld
Markus
M
Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str 10, 13125 Berlin, Germany.
Puentes
Fabiola
F
Borsellino
Giovanna
G
Battistini
Luca
L
Rötzschke
Olaf
O
Falk
Kirsten
K
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D007156:Immunologic Memory / Q000502:physiology*; D016753:Interleukin-10 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D051379:Mice; D010641:Phenotype; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000235:genetics* / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
C493447:CCL20 protein, mouse; C498126:CCR6 protein, mouse; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D015375:Receptors, Interleukin-2; D016753:Interleukin-10; D017493:Leukocyte Common Antigens