IL-2Rbeta links IL-2R signaling with Foxp3 expression.

Immunological tolerance to self antigens is a tightly regulated process. Recent work has demonstrated that the forkhead family member Foxp3 is a critical element in the differentiation and function of mouse CD4(+)CD25(+) regulatory T cells (Treg). Recent work has suggested an important role for IL-2 in the development and maintenance of Treg.

Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance.

Emerging evidence suggests critical roles for APCs in suppressing immune responses. Here, we show that zymosan, a stimulus for TLR2 and dectin-1, regulates cytokine secretion in DCs and macrophages to induce immunological tolerance. First, zymosan induces DCs to secrete abundant IL-10 but little IL-6 and IL-12(p70).

Cutting Edge: Anti-CD25 monoclonal antibody injection results in the functional inactivation, not depletion, of CD4+CD25+ T regulatory cells.

CD4+CD25+ T regulatory (T(R)) cells are an important regulatory component of the adaptive immune system that limit autoreactive T cell responses in various models of autoimmunity. This knowledge was generated by previous studies from our lab and others using T(R) cell supplementation and depletion. Contrary to dogma, we report here that injection of anti-CD25 mAb results in the functional inactivation, not depletion, of T(R) cells, resulting in exacerbated autoimmune disease.

Dynamic regulation of FoxP3 expression controls the balance between CD4+ T cell activation and cell death.

The forkhead-family transcription factor FoxP3 is important for the development and function of CD4+CD25+ regulatory T cells. While the overall phenotypic effects of FoxP3 expression are evident, the mechanism by which FoxP3 regulates T cell activation is not well understood. CD4+ T cells from mice that express a FoxP3 Tg are refractory to TCR-mediated stimulation, failing to proliferate or produce cytokines, but possess suppressive activity towards normal T cells.

Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells.

CD4+CD25+ regulatory T (TR) cells have been described in both humans and mice. In mice, TR are thymically derived, and lack of TR leads to organ-specific autoimmunity. Recently, the forkhead/winged helix transcription factor, FoxP3, has been shown to be important for the function of TR cells in mice.

Scurfin (FoxP3) controls T-dependent immune responses in vivo through regulation of CD4+ T cell effector function.

Scurfin, the protein product of the FoxP3 gene, is a forkhead-family transcription factor that negatively regulates T cell function. Mice carrying a loss-of-function mutation in FoxP3 (scurfy mice) present with fatal autoimmune-like disease caused by hyperresponsive CD4(+) T cells. Mice that overexpress scurfin (FoxP3 Tg mice) possess fewer mature T cells with reduced functional capabilities compared with normal littermate control mice.

Adaptive immunity in mice lacking the beta(2)-adrenergic receptor.

The beta-2-adrenergic receptor (beta(2)AR) is expressed by most lymphocyte populations and binds the sympathetic neurotransmitter norepinephrine (NE). Stimulation of the beta(2)AR is reported to be the primary mechanism by which signals from the sympathetic nervous system influence both cell-mediated and humoral immunity. We report here that body/organ weights, lymphoid organ cell number/phenotype/histology, the contact sensitivity response, and the amount, avidity, and isotype of antibody resulting from a T cell-dependent antibody response in beta(2)AR deficient mice (beta(2)AR-/- mice) were all similar to measures made in beta(2)AR+/+ mice.

The generation of mature, single-positive thymocytes in vivo is dysregulated by CD69 blockade or overexpression.

During development in the thymus, mature CD4+ or CD8+ cells are derived from immature CD4+CD8+ cells through a series of selection events. One of the hallmarks of this maturation process is the expression of CD69, which first appears on thymocytes as they begin positive selection. We have used blockade and overexpression of CD69 to determine the role of CD69 in thymocyte development.