The glucocorticoid-induced TNFR family-related protein (GITR, TNFRSF18, CD357) is expressed on effector and regulatory T (Treg) cells. Previous studies demonstrated that GITR triggering by anti-GITR mAb enhanced T and B cell-mediated immune responses. GITR-deficient T cells, however, also proliferate more than normal T cells, and this effect is unexplained. Because the activities of mAbs are co...

Although high mobility group box 1 (HMGB1) in tumor cells is involved in many aspects of tumor progression, its role in tumor immune suppression remains elusive. Host cell-derived IL-10 suppressed a naturally acquired CD8 T cell-dependent antitumor response. The suppressive activity of tumor-associated Foxp3 + CD4 + CD25 + regulatory T cells (Treg) was IL-10 dependent. Neutralizing HMGB1 impair...

Gut commensal microbes affect the mucosal immune system via expansion of regulatory T cells (Treg) in colon. This is mediated short-chain fatty acids (SCFA), bacterial metabolites generated during fiber fermentation. SCFA are also produced by skin bacteria and may activate resident Treg, activity which diminished certain inflammatory dermatoses. Only upon binding to G-protein coupled receptors,...

Regulatory T cells (Treg) restrain skin inflammation under healthy conditions and after immune challenges. Adult human contains 20 billion 1-3 are highly suppressive FOXP3+ Treg. We observed inflammatory eruptions in CTCL patients treated with alemtuzumab (αCD52), an antibody that purges recirculating from skin. αCD52-induced eczematous dermatitis had 5-fold lower Treg numbers (p<0.0001) 7-fold...

Maintaining immune tolerance requires the production of Foxp3-expressing regulatory T (Treg) cells in the thymus. Activation of NF-κB transcription factors is critically required for Treg cell development, partly via initiating Foxp3 expression. NF-κB activation is controlled by a negative feedback regulation through the ubiquitin editing enzyme A20, which reduces proinflammatory signaling in m...

We previously developed methods for establishing CD8 regulatory T cell (Treg) clones from normal human peripheral blood and demonstrated that these clones were capable of killing T cell receptor (TCR)-activated autologous CD4 T cells. Based on phenotypic and functional characterization of the CD8 Treg clones, we have identified a corresponding population of endogenous CD8 Treg in normal human p...

T he secondary neuroinflammatory response has attracted increasing attention in experimental stroke research. 1 Analyses of immunologic mechanisms after acute stroke have been performed in the hope of identifying key pathomecha-nisms that contribute to secondary infarct growth and can be modulated to benefit a large proportion of patients with stroke. Among a variety of pathophysiologic mechani...

Transplants tolerated through a process known as infectious tolerance evoke continuous recruitment of regulatory T (Treg) cells that are necessary to maintain the unresponsive state. This state is maintained long-term and requires continuous Ag exposure. It is not known, however, whether infectious tolerance operates through sustained recruitment of pre-existing regulatory cells, induction of r...

The exact role of adult thymus in autoimmune disease state is poorly understood. We show here that thymus regulated experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, as evidenced by loss of spontaneous recovery in thymectomized EAE mice. There was progressive enrichment for CD4 single-positive Foxp3(+) regulatory T cells in thymocytes during the course of ...

Introduction Regulatory T cells (Treg) are crucial for maintaining immune homeostasis and mediating immune tolerance. Besides their immune regulatory function, Treg can produce pro-inflammatory cytokines such as interleukin (IL)-17 and interferon (IFN)-g. Recently, our group has identified CD161 as a marker for pro-inflammatory FoxP3+ T cells which have classic Treg characteristics but also hav...