Inhibition of differentiation, amplification, and function of XXXX TH17 cells by intravenous immunoglobulin.

@entity1 @entity650 @entity404 @entity1356 @entity4104 @entity15787 @entity4155 @entity2533 @entity56 @entity4654 @entity16365 @entity1968
BACKGROUND: T(H)17 cells play a critical role in the pathogenesis of several autoimmune and @entity56 . Intravenous immunoglobulin (IVIg), a therapeutic preparation of polyclonal IgG that is increasingly used in the treatment of diverse autoimmune and @entity56 , might target T(H)17 cells to exert therapeutic effects. OBJECTIVE: We sought to examine whether IVIg interferes with the development and function of @entity1 T(H)17 cells. METHODS: T(H)17 cells were differentiated from naive @entity1 @entity404 (+) T cells in the presence of @entity2533 and @entity15787 . T(H)17 cells were amplified by stimulating memory @entity404 (+) T cells in the presence of @entity1356 and @entity650 . The effect of IVIg was examined on the differentiation and amplification of T(H)17 cells, expression of the T(H)17 lineage-specific transcription factor @entity1968 -related orphan receptor C, secretion of T(H)17 effector cytokines, and phosphorylation of @entity4104 , a transcription factor that plays an important role in T(H)17 cell development and function. RESULTS: IVIg inhibits the differentiation and amplification of @entity1 T(H)17 cells, as well as the production of their effector cytokines @entity4155 , @entity4654 , @entity15787 , and @entity16365 . The inhibitory effects of IVIg on T(H)17 cells are F(ab')(2) dependent and involve interference with the expression of @entity1968 -related orphan receptor C and activation of @entity4104 . Also, IVIg significantly enhanced forkhead box protein 3-positive regulatory T cells among the memory @entity404 (+) T cells. CONCLUSION: These results reveal a novel mechanism of action of IVIg in achieving a therapeutic effect in autoimmune and @entity56 , in which T(H)17 cells play a key modulatory role in sustaining the chronic inflammatory response. Our results also suggest a reciprocal regulation of T(H)17 and regulatory T-cell populations by IVIg.
