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Foxp3(+) CD4(+) CD25(+) regulatory cell (Treg) subsets that maintain immunologic homeostasis have been considered to be a homogeneous population of naturally occurring, thymus-derived CD4(+)CD25(+) cells (nTregs). However, similar Foxp3+ Tregs can be induced from CD25(-) precursors in vivo, and ex vivo with interleukin 2 (IL-2) and transforming growth(More)
IL-2 and TGF-beta both have important roles in the induction and maintenance of immunologic tolerance, but whether these cytokines act separately or together to achieve this effect is poorly understood. Although others have reported that IL-2 can directly enhance forkhead box protein P3 (Foxp3) transcription factor expression by natural CD4(+)CD25(+)(More)
CD4+Foxp3+ Treg consist of two indistinguishable subsets induced in either the thymus or the periphery. In addition to their suppressive activities, IL-6 can convert natural Treg to pro-inflammatory IL-17-producing cells, but those induced with IL-2 and TGF-beta remain Treg. Unlike mouse CD4+CD25(-) cells, which rapidly become polyclonal Foxp3+CD25+ Treg(More)
Thymus-derived, natural CD4(+)CD25(+) regulatory T cells can educate peripheral CD4(+)CD25(-) cells to develop suppressive activity by poorly understood mechanisms. TGF-beta has IL-2-dependent costimulatory effects on alloactivated naive, human CD4(+) T cells and induces them ex vivo to become potent contact-dependent, cytokine-independent suppressor cells.(More)
TGF-beta has pleiotropic effects on T cell differentiation that are determined by other cytokines in the local environment. Whereas IL-2 and TGF-beta induce naive T cells to become forkhead/winged helix transcription factor (Foxp3) positive regulatory cells (iTregs), the combination of IL-6 and TGF-beta induces IL-17-producing cells (Th17). Moreover, IL-6(More)
Previously we reported that TGF-beta has an important role in the generation and expansion of human "professional" CD4(+)CD25(+) regulatory T cells in the periphery that have a cytokine-independent mechanism of action. In this study we used low-dose staphylococcal enterotoxin to induce T cell-dependent Ab production. We report that TGF-beta induces(More)
Regulatory T cells generated ex vivo from conventional mouse T cells have been used to prevent and alter the course of a stimulatory graft-vs-host disease with a lupus-like syndrome. DBA/2 mouse T cells induce this syndrome when injected into (DBA/2 x C57BL/6) F(1) mice. Stimulating DBA/2 T cells with irradiated C57BL/6 in the presence of IL-2 and TGF-beta(More)
It has been well recognized that a deficit of numbers and function of CD4+CD25+Foxp3+ cells (Treg) is attributed to the development of some autoimmune diseases; however, there are controversial data regarding the suppressive effect of Treg cells on the T cell response in systemic lupus erythematosus (SLE). Additionally, IL-17-producing cells (Th17) have(More)
TNF-alpha has both proinflammatory and immunoregulatory functions. Whereas a protective role for TNF administration in systemic lupus erythematosus (SLE)-prone (New Zealand Black x New Zealand White)F(1) mice has been established, it remains uncertain whether this effect segregates at the individual TNFR. We generated SLE-prone New Zealand Mixed 2328 mice(More)
BACKGROUND BAFF, in addition to promoting B cell survival and differentiation, may affect T cells. The objective of this study was to determine the effect of BAFF on Th17 cell generation and its ramifications for the Th17 cell-driven disease, EAE. METHODOLOGY/PRINCIPAL FINDINGS Th17 cells were increased in BAFF-Tg B6 (B6.BTg) mice and decreased in(More)