Inducible costimulator (ICOS) is a marker for highly suppressive antigen-specific T cells sharing features of TH17/TH1 and regulatory T cells.
BACKGROUND
CD4(+)CD25(+) regulatory T (Treg) cells are involved in the downmodulation of numerous immune responses to pathogens, tumors, or allergens.


OBJECTIVE
In this study, we further characterized the nature of Treg cells that control skin inflammatory reactions to haptens.


METHODS
In a model of contact hypersensitivity to 2,4-dinitro-fluorobenzene, we have investigated the phenotype, the specificity, and the origin of Treg cells that modulate the priming of effector CD8(+) T cells responsible for the development of the pathology.


RESULTS
2,4-Dinitrofluorobenzene immunization induced a population of CD4(+)CD25(+) Treg cells that controlled CD8(+) T-cell effector responses in a hapten-specific manner in vivo. High levels of inducible costimulator (ICOS) expression defined a population of CD4(+)CD25(+)FoxP3(+) (forkhead box protein 3) Treg cells that presented superior suppressive activity. Importantly, ICOS(+) Treg cells were distinguishable from all other FoxP3(+) Treg cells by the expression of IL-10, IL-17, and IFN-gamma. Hapten-specific Treg cells proliferating in response to their cognate antigen in vivo predominantly displayed a CD25(+)FoxP3(+)ICOS(+) phenotype. By using reporter mice, we showed that ICOS(+) Treg cells derived from the expansion of natural CD4(+)FoxP3(+) Treg cells rather than generation of adaptive Treg cells. Furthermore, the generation of ICOS(+) Treg cells depended on innate cells rather than the effector CD8(+) T-cell population.


CONCLUSIONS
Taken together, our data show that a population of CD4(+)CD25(+)FoxP3(+) T cells upregulates ICOS on in vivo sensitization and specifically suppresses hapten-reactive CD8(+) T cells both in vivo and in vitro.
Vocanson
Marc
M
Université Lyon1, Faculté de Médecine Lyon Sud, Lyon, France.
Rozieres
Aurore
A
Hennino
Anca
A
Poyet
Gaelle
G
Gaillard
Vincent
V
Renaudineau
Sarah
S
Achachi
Amine
A
Benetiere
Josette
J
Kaiserlian
Dominique
D
Dubois
Bertrand
B
Nicolas
Jean-François
JF
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism; D004139:Dinitrofluorobenzene / Q000009:adverse effects / Q000494:pharmacology; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D006241:Haptens / Q000009:adverse effects / Q000494:pharmacology; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D060889:Inducible T-Cell Co-Stimulator Protein; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006241:Haptens; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D004139:Dinitrofluorobenzene