We investigated the association between cellular immunity and age-related hearing loss (ARHL) development using three CD4+ T cell fractions, namely, naturally occurring regulatory cells (Treg), interleukin 1 receptor type 2-expressing (I1R2), non-Treg non-I1R2 (nTnI) cells, which comprised Treg I1R2-deleted cells. Inoculation of nTnI fraction into a ARHL murine model, not only prevented degener...

Regulatory T (Treg) cells are found at elevated densities in many human cancers and are thought to be a major barrier to the generation of robust antitumor T cell responses. In this review, we discuss recent advances in the understanding of tumor-associated Treg cell diversity and function. Emerging evidence indicates that the transcriptional program of Treg cells infiltrating human cancers may...

Granzyme B is important for the ability of NK cells and CD8(+) T cells to kill their targets. However, we showed here that granzyme B-deficient mice clear both allogeneic and syngeneic tumor cell lines more efficiently than do wild-type (WT) mice. To determine whether regulatory T (Treg) cells utilize granzyme B to suppress immune responses against these tumors, we examined the expression and f...

The transcription factor Foxp3 dominantly controls regulatory T (Treg) cell function, and only its continuous expression guarantees the maintenance of full Treg cell-suppressive capacity. However, transcriptional regulators maintaining Foxp3 transcription are incompletely described. Here, we report that high E47 transcription factor activity in Treg cells resulted in unstable Foxp3 expression. ...

The interplay between effector and regulatory T (Treg) cells is crucial for adaptive immunity, but how Treg control diverse effector responses is elusive. We found that the phosphatase PTEN links Treg stability to repression of TH1 and TFH (follicular helper) responses. Depletion of PTEN in Treg resulted in excessive TFH and germinal center responses and spontaneous inflammatory disease. These ...

Recent studies and our current data demonstrated the deficits in the numbers and/or functions of the CD4(+)CD25(+)Foxp3(+) Treg cells in the patients with autoimmune diseases, indicating that restoration of Treg cells in these patients could be a potential therapeutic approach. Here, we demonstrated that CD4(+)CD25(+)Foxp3(+) Treg cells can be purified, activated and expanded from peripheral bl...

A balance between Th17 and regulatory T (Treg) cells is critical for immune homeostasis and tolerance. Our previous work has shown Serum- and glucocorticoid-induced kinase 1 (SGK1) is critical for the development and function of Th17 cells. Here, we show that SGK1 restrains the function of Treg cells and reciprocally regulates development of Th17/Treg balance. SGK1 deficiency leads to protectio...

Regulatory T cells (Treg) play a dominant role in suppression of autoimmune pathology, as rescue of Treg number and/or function in model systems can both prevent and reverse disease. These findings have generated a series of studies addressing the role of defects in Treg number and function in human autoimmunity. However, demonstrating global defects in Treg of individuals diagnosed with autoim...

CD4+CD25+ regulatory T cells (Treg) are potent immunosuppressive cells that are pivotal in the regulation of peripheral tolerance. In this report, we identify granzyme B (GZ-B) as one of the key components of Treg-mediated suppression. Induction of regulatory activity is correlated with the up-regulation of GZ-B expression. Proof of a functional involvement of GZ-B in contact-mediated suppressi...

Accumulation of T regulatory (Treg) cells within the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE) is essential for the resolution of disease. CNS Treg cells have been shown to uniformly express the Th1-associated molecules, T-bet and CXCR3. Here, we report that the expression of T-bet is not required for the function of these Treg within the CNS. Using mic...