The origin of thymic XXXX +CD25+ regulatory T cells and their co-stimulatory requirements are determined after elimination of recirculating peripheral @entity1961 + cells.

@entity19 @entity17796 @entity1961 @entity4458 @entity6553 @entity164 @entity3744
Studies on the thymic ontogeny of naturally arising @entity1961 (+)CD25(+) regulatory T cells (TR cells) are complicated by the contamination of recirculating cells from the periphery (both activated @entity1961 (+) T and TR cells). We investigated TR cells in anti- @entity1961 antibody transgenic (Tg) (GK) @entity19 that continuously deplete peripheral @entity1961 T cells but not thymocytes so that the generation of thymic TR cells and their developmental requirement can be accurately assessed. We show that in the thymuses of @entity19 that lack peripheral @entity1961 (+) cells, TR cells were present but were fewer in number compared with @entity164 ( @entity164 ) @entity19 . Therefore, we show that peripheral TR cells do re-enter the thymus, comprising 20% of TR cells in the normal thymus. TR cells from both @entity164 and GK @entity19 expressed @entity3744 and @entity6553 , and suppressed the proliferation of CD25(-) @entity1961 (+) T cells. Furthermore, the co-stimulation requirements for TR generation were evaluated in @entity19 with or without peripheral @entity1961 cells. Splenic TR cells in @entity4458 (-/-) @entity19 and @entity17796 Ig Tg @entity19 were fewer compared with @entity164 @entity19 . @entity19 deficient in both co-stimulatory pathways had further reduction in splenic TR cells. Unlike the periphery, the reduction in thymic TR cells was only seen for @entity4458 (-/-) but not for @entity17796 Ig Tg @entity19 . Therefore, we found that the co-stimulation requirements for the thymic development of TR cells differed from those for peripheral homeostasis.
