title: Maturation of human dendritic cells with Saccharomyces cerevisiae (yeast) reduces the number and function of regulatory T cells and enhances the ratio of antigen-specific effectors to regulatory T cells.
abstract: We compared the effects of yeast-treated human dendritic cells (DCs) with CD40L-matured human DCs for the induction of effector cells and the number and functionality of CD4(+)CD25(+)CD127(-)FoxP3(+) regulatory T cells (Tregs). DCs were treated with yeast or CD40L and cocultured with isolated autologous CD4(+) T cells. CD4(+)CD25(+)CD127(-) T cells isolated from the coculture of CD4(+) T cells plus yeast-treated DCs (yeast coculture) had a lower expression of FoxP3 and decreased suppressive function compared to CD4(+)CD25(+)CD127(-) T cells isolated from the coculture of CD4(+) T cells plus CD40L-treated DCs (CD40L coculture). Also, compared to the CD40L coculture, the yeast coculture showed increases in the ratio of CD4(+)CD25(+) activated T cells to Tregs and in the production of Th1-related cytokines (IL-2, TNF-α, IFN-γ) and IL-6. In addition, yeast-treated DCs used as antigen-presenting cells (APCs) incubated with the tumor antigen CEA enhanced the proliferation of CEA-specific CD4(+) T cells compared to the use of CD40L-matured DCs used as APCs. This is the first study to report on the role of yeast-treated/matured human DCs in reducing Treg frequency and functionality and in enhancing effector to Treg ratios. These results provide an additional rationale for the use of yeast as a vector in cancer vaccines.
authors.affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Vittore
authors.initials: V
authors.lastname: Cereda
authors.forename: Matteo
authors.initials: M
authors.lastname: Vergati
authors.forename: Ngar-Yee
authors.initials: NY
authors.lastname: Huen
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: di Bari
authors.forename: Caroline
authors.initials: C
authors.lastname: Jochems
authors.forename: Chiara
authors.initials: C
authors.lastname: Intrivici
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.forename: David
authors.initials: D
authors.lastname: Apelian
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: Kwong Y
authors.initials: KY
authors.lastname: Tsang
mesh_terms: D000946:Antigens, Fungal / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis; D012441:Saccharomyces cerevisiae / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000946:Antigens, Fungal; D015704:CD4 Antigens; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D023201:CD40 Ligand