OBJECTIVE: @entity32 and @entity5 development are associated with dysregulated immune responses and the presence of regulatory T cells (T(reg)). To study the role of T(reg) in @entity5 cell escape from immune surveillance, an in vitro model simulating the @entity5 microenvironment and promoting the induction and expansion of @entity688 (+) T(reg )type 1 (Tr1) was established. METHODS: An in vitro co-culture system ( @entity3480 ) included an @entity135 and @entity213 cell line, immature dendritic cells (iDC), @entity404 (+)CD25(- )T cells and cytokines, @entity1199 (10 IU/ml), @entity688 (20 IU/ml), @entity8252 (20 IU/ml) +/- 1 nM @entity3446 . Autologous iDC and @entity404 (+)CD25(-) T cells were obtained from the peripheral blood of 15 normal donors. Co-cultures were expanded for 10 days. Proliferating lymphocytes were phenotyped by multi-color flow cytometry. Their suppressor function was measured in CFSE inhibition assays +/- neutralizing anti- @entity688 mAb and using transwell cultures. Culture supernatants were tested for @entity3646 , @entity688 , @entity2533 and @entity379 in ELISA. RESULTS: In the @entity3480 , low doses of @entity1199 , @entity688 and @entity8252 promoted induction and expansion of CD3(+) @entity404 (+)CD25(-) @entity3647 (+)IL2Rgamma(+) @entity403 (+) @entity688 (+) cells with suppressor activity (mean suppression +/- SD = 58 +/- 12%). These suppressor cells produced @entity688 (mean +/- SD = 535 +/- 12 pg/ml) and @entity2533 (mean +/- SD = 512 +/- 38 pg/ml), but no @entity3646 or @entity379 . Suppressor function of co-cultures correlated with the percent of expanding @entity688 (+) Tr1 cells (r (2 )=( )0.9; P < 0.001). The addition of @entity3446 enriched Tr1 cells in all co-cultures. Neutralizing anti- @entity688 mAb abolished suppressive activity. Suppression was cell-contact independent. CONCLUSION: The @entity5 microenvironment promotes generation of Tr1 cells which have the phenotype distinct from that of @entity404 (+)CD25(high) @entity403 (+) nTreg and mediate @entity688 dependent immune suppression in a cell-contact independent manner. Tr1 cells may play a critical role in @entity5 progression.

Expansion and characteristics of human T regulatory type 1 cells in co-cultures simulating XXXX microenvironment.

@entity32 :: ('MESH:D007249', 'Disease') :: ['Chronic inflammation'] @entity135 :: ('MESH:D006258', 'Disease') :: ['irradiated head'] @entity3647 :: ('3560', 'Gene') :: ['IL2Rbeta'] @entity404 :: ('920', 'Gene') :: ['CD4'] @entity3480 :: ('MESH:C538167', 'Disease') :: ['IVA'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity3446 :: ('MESH:D020123', 'Chemical') :: ['rapamycin'] @entity3646 :: ('3565', 'Gene') :: ['IL-4'] @entity2533 :: ('7040', 'Gene') :: ['TGF-beta'] @entity379 :: ('3458', 'Gene') :: ['IFN-gamma'] @entity403 :: ('50943', 'Gene') :: ['FoxP3'] @entity1199 :: ('3558', 'Gene') :: ['IL-2'] @entity8252 :: ('3600', 'Gene') :: ['IL-15'] @entity688 :: ('3586', 'Gene') :: ['CTLA-4(+)IL-10', 'IL-10'] @entity213 :: ('MESH:C535575', 'Disease') :: ['neck squamous cell carcinoma']
@entity5 :: (MESH:D009369,Disease) :: ['tumor']
