This paper introduces a model which incorporates fetal thymus organ culture (FTOC) from NOD @entity19 to replicate thymic development of @entity1619 cells. NOD fetal pancreas organ culture (FPOC) co-cultured with 13-16 day NOD FTOC for an additional 14-21 days produced less insulin than FPOC cultured alone. Insulin production from the FTOC of non-diabetic strains C57BL/6 and BALB/c was not inhibited by co-culture with FTOC from their syngeneic counterparts. Sections of the NOD co-cultures showed peri-islet infiltration with lymphocytes. Insulin reduction by FTOC/FP co-culture was prevented by co-culture of the NOD FT with FT from immunologically incompetent C.B-17 @entity915 / @entity915 @entity19 . Co-culture of NOD FP with NOD FT prior to the development of T cells prevented generation of diabetogenic FTOC. Thus, early exposure of NOD T cell precursors to the thymic stromal elements of C.B-17 @entity915 / @entity915 FT or to islet antigens can negatively select for @entity1619 cells or activate immuno-regulatory cells that can suppress @entity1619 cell activity. The addition of blocking F(ab')2 fragments of anti- @entity5168 monoclonal antibody to NOD FTOC/FP co-cultures prevented insulin reduction, implicating a role for @entity12810 -mediated recognition in this "in vitro @entity1723 " model. The addition of activating whole anti- @entity5168 caused the complete ablation of insulin production in FTOC/FP co-cultures from all strains tested. Transfer of unprimed syngeneic FTOC cells to prediabetic NOD @entity19 prevented the onset of @entity1723 while transfer of islet-cell primed FTOC/FP cells slightly increased disease incidence. These data suggest that while @entity1619 cells are present in the FT, they are normally suppressed, even after organ culture. However, these cells can induce the destruction of islet cells, in vitro and in vivo, if they are appropriately activated with pancreatic tissue.

NOD fetal thymus organ culture: an in vitro model for the development of T cells involved in XXXX .

@entity1619 :: ('MESH:D015458', 'Disease') :: ['diabetogenic T'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity5168 :: ('12501(Tax:10090)', 'Gene') :: ['CD3epsilon'] @entity12810 :: ('328483(Tax:10090)', 'Gene') :: ['TcR'] @entity915 :: ('MESH:D053632', 'Disease') :: ['SCID'] @entity1723 :: ('MESH:D003922', 'Disease') :: ['IDDM']
@entity1723 :: (MESH:D003922,Disease) :: ['IDDM']
