Polyfunctional, Pathogenic XXXX + Th17 Lineage Cells Are Resistant to Regulatory T Cell-Mediated Suppression in the Context of Autoimmunity.

@entity32 @entity21319 @entity4104 @entity519 @entity792 @entity403 @entity4386 @entity13796 @entity309
UNASSIGNED: In @entity792 such as @entity309 ( @entity309 ), regulatory T cells (Tregs) fail to constrain @entity32 ; however, the reasons for this are unclear. We investigated T cell regulation in the @entity309 joint. Tregs from @entity309 synovial fluid suppressed autologous responder T cells; however, when compared with Tregs from healthy control peripheral blood, they were significantly less suppressive. Despite their reduced suppressive activity, Tregs in the @entity309 joint were highly proliferative and expressed @entity403 , @entity13796 , and @entity4386 , which are markers of functional Tregs. This suggested that the reduced suppression is due to resistance of @entity309 synovial fluid responder T cells to Treg inhibition. @entity21319 (+) Th17 lineage cells were significantly enriched in the @entity309 joint; we therefore investigated their relative susceptibility to Treg-mediated suppression. Peripheral blood @entity21319 (+) Th cells from healthy controls were significantly more resistant to Treg-mediated suppression, when compared with @entity21319 (-) Th cells, and this was mediated through a @entity4104 -dependant mechanism. Furthermore, depletion of @entity21319 (+) Th cells from the responder T cell population in @entity309 synovial fluid restored Treg-mediated suppression. In addition, @entity21319 (+) Th cells exhibited pathogenic features, including polyfunctional proinflammatory cytokine production, an ability to activate synovial fibroblasts, and to survive and persist in the inflamed and @entity519 joint. Because @entity21319 (+) Th cells are known to be enriched at sites of autoinflammation, our finding that they are highly proinflammatory and resistant to Treg-mediated suppression suggests an important pathogenic role in @entity309 and other @entity792 .
