CD4+ T cells treated with TNFalpha blocking agents during activation.

ABSTRACT: Objective. TNF? is a potent pro-inflammatory cytokine playing a pivotal role in several autoimmune diseases. Neutralizing TNF? inhibits T cell proliferation and IFN? production, and enhances suppressive capacity of regulatory T cells (Treg). Little is known about the mechanism of TNF? blocking agents on naïve T cell differentiation. Methods. Naïve CD4+ T cells were activated by dendritic cells (DC) in presence or absence of anti-TNF? agents. T cell polarization and activation was assessed during T cell differentiation. In addition, whole genome gene expression analysis was performed on anti-TNF?-treated T cells. Results. Neutralizing TNF? during priming of naïve CD4+ T cells by DC favors development of IL-10+ T helper (Th) cells at the expense of IFN? induction. TNF? inhibits IL-10 via TNFRII, which becomes expressed after naïve T cell activation. While initial CD4+ T cell activation was not affected, neutralization of TNF? negatively affected later stages of T cell priming by counteracting full T cell activation and survival. Whole genome gene expression analysis revealed a regulatory gene profile of anti-TNF?-treated T cells. Indeed, neutralizing TNF? during naïve T cell priming enhanced the suppressive function of anti-TNF?-treated T cells. Conclusion. Inhibition of TNF?–TNFRII interaction affects late stage effector T cell development and shifts the balance of Th cell differentiation towards IL-10 expressing regulatory T cells, which may be one of the beneficial mechanisms in TNF? blocking therapies. Naïve CD4+ T cells were CFSE labeled and co-cultured for 13 days with allogeneic dendritic cells in the presence or absence of anti-TNF? agents. After 13 days, the CFSElow T cells were FACS sorted. Samples were generated from three independent donors.

ORGANISM(S): Homo sapiens

SUBMITTER: Martine Boks 

PROVIDER: E-GEOD-42812 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress