CD40 ligand in pathogenesis of XXXX of day 3-thymectomized @entity19 : implication for CD40 ligand antibody therapy.

@entity32 @entity26490 @entity19 @entity60 @entity3783 @entity1961 @entity4458 @entity2670 @entity792 @entity3844 @entity6232
The blockade of @entity4458 ( @entity4458 ) is effective in @entity792 prevention. Recently, a brief period of @entity4458 mAb treatment was reported to induce tolerance and enhancement of @entity1961 (+) @entity3783 (+) regulatory T cell activity. We therefore determined the efficacy of @entity4458 mAb treatment in autoimmunity that resulted from @entity1961 (+) @entity3783 (+) regulatory T cell deficiency. @entity2670 ( @entity2670 ) and oocyte autoantibody response of day 3-thymectomized (d3tx) @entity19 were inhibited by continuous @entity4458 mAb treatment from day 3, or from days 10-14, whereas @entity4458 mAb treatment confined to the neonatal week was ineffective. The enhanced expression of memory markers ( @entity3844 and @entity6232 (low)) on @entity1961 (+) T cells of the d3tx @entity19 was unaffected by @entity4458 mAb treatment. In contrast, their increased T cell activation markers ( @entity26490 and @entity3783 ) were eliminated by @entity4458 mAb treatment. Moreover, ex vivo activated T cells of d3tx @entity19 expressed elevated intracellular @entity60 , and this was also blocked by @entity4458 mAb. The memory T cells, although nonpathogenic in @entity4458 mAb-positive environment, transferred severe @entity2670 to @entity4458 mAb(-) neonatal recipients. Most importantly, @entity4458 mAb treatment inhibited @entity2670 in recipients of T cells from d3tx donors with severe @entity2670 and led to regression of @entity2670 in d3tx @entity19 documented at 4 wk. Therefore, 1) the continuous presence of @entity4458 mAb both prevents and causes regression of @entity2670 in the d3tx @entity19 ; and 2) the multiple steps of the d3tx @entity792 , including T cell activation, cytokine production, T cell-mediated @entity32 , and tissue injury, are @entity4458 dependent.
