title: Regulatory T cells target chemokine secretion by dendritic cells independently of their capacity to regulate T cell proliferation.
abstract: The clinical manipulation of regulatory T cells (Tregs) represents a promising strategy for the regulation of unwanted immune responses. It is now becoming clear that Tregs exert multiple effects on different cell targets under particular conditions; however, the interplay between these different factors remains unclear. Using mouse Tregs of known Ag specificity, we report in this study two different levels of Treg-mediated suppression: one that targets T cell proliferation and one that targets dendritic cell-mediated proinflammatory chemokine (CCL3 and CCL4) production. These two effects can be dissociated, and whereas modulation of T cell proliferation depends on the strength of the antigenic stimulus, modulation of chemokine production by dendritic cells does not. We also provide evidence that the bystander effect of Tregs on immune responses observed in vivo may be in great part explained by a decrease in the recruitment of target T cells, and therefore in the magnitude of the response, rather than by a direct effect on their priming or proliferation. Overall, our results shed some light on the different aspects that need to be considered when attempting to modulate Tregs for clinical purposes.
authors.affiliation: Istituto Clinico Humanitas, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Morlacchi
authors.forename: Valentina
authors.initials: V
authors.lastname: Dal Secco
authors.forename: Cristiana
authors.initials: C
authors.lastname: Soldani
authors.forename: Nicolas
authors.initials: N
authors.lastname: Glaichenhaus
authors.forename: Antonella
authors.initials: A
authors.lastname: Viola
authors.forename: Adelaida
authors.initials: A
authors.lastname: Sarukhan
mesh_terms: D000818:Animals; D024201:Bystander Effect / Q000276:immunology; D049109:Cell Proliferation; D054405:Chemokine CCL3 / Q000378:metabolism; D054407:Chemokine CCL4 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D007109:Immunity; D051379:Mice; D013601:T-Lymphocytes / Q000166:cytology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines