Dynamics of peripheral tolerance and immune regulation mediated by Treg

Abstract

Peripheral self-tolerance and immune homeostasis are maintained, at least in part, by the balance between Treg and effector T cells. Naturally, arising CD25 1 CD41 Treg, which express the transcription factor Foxp3, suppress the activation and proliferation of other lymphocytes in multiple ways. A CTLA-4-dependent suppressive mechanism is shared by every Foxp3 1 Treg at any location and its disruption breaches self-tolerance and immune homeostasis, suggesting that it is a core mechanism of suppression. Depending on the environment, Foxp3 1 Treg also differentiate to exhibit additional suppressive mechanisms, including the secretion of immunosuppressive cytokines. Naïve T cells acquire Foxp3 expression and suppressive activity under certain in vivo and in vitro conditions, whereas some Foxp3 1 T cells may lose Foxp3 and suppressive activity following proliferation in an IL-2-deficient environment. Moreover, activated effector T cells frequently secrete suppressive cytokines, such as IL-10, in a negative feedback fashion. These findings, when taken together, indicate that peripheral immune tolerance and homeostasis are dynamically maintained by functional differentiation within the Foxp3 1 population, occasional conversion between Treg and non-Treg cells, and the interactions among them. These dynamics provide ample opportunities for immune intervention for the benefit of the host.

SATB1 Plays a Critical Role in Establishment of Immune Tolerance

“…Once immune tolerance is disturbed, the bodies' immune system may attack itself and various organs may get damaged, resulting in autoimmune diseases (44). Treg cells, which are CD4 + T cells that express the transcription factor Foxp3, play a central role in establishment of peripheral tolerance and immune homeostasis (45). Treg cell deficiency and dysfunction may cause a T cell-mediated autoimmune disorder (45).…”

“…Treg cells, which are CD4 + T cells that express the transcription factor Foxp3, play a central role in establishment of peripheral tolerance and immune homeostasis (45). Treg cell deficiency and dysfunction may cause a T cell-mediated autoimmune disorder (45). Therefore, to determine the involvement of Tregs in the autoimmunity of the SATB1cKO mice, we first compared the frequency and the cell number of splenic Treg cells in SATB1cKO mice with those of WT littermates.…”

Selective Depletion of Foxp3+ Regulatory T Cells Improves Effective Therapeutic Vaccination against Established Melanoma

“…Regulatory T cells (Treg) play an essential role in modulating host responses to tumors and infections, in preventing transplant rejection, and in inhibiting the development of autoimmunity and allergy (1)(2)(3). Originally, CD4 + Tregs were identified by the constitutive expression of CD25, however, both the existence of CD25 − Tregs as well as the expression of CD25 on activated conventional T cells limits the use of this marker (3).…”

“…Originally, CD4 + Tregs were identified by the constitutive expression of CD25, however, both the existence of CD25 − Tregs as well as the expression of CD25 on activated conventional T cells limits the use of this marker (3). Currently, the most widely used and reliable Treg marker is the forkhead box transcription factor Foxp3, which is expressed specifically in murine CD4 + Tregs and which is essential for their lineage identity and suppressive function (4)(5)(6)(7)(8).…”

Role of regulatory T cells in rheumatoid arthritis: facts and hypothesis

“…The hypothesis that Treg cells could be involved in the pathogenesis of autoimmune diseases led to subsequent investigations not only in animal models with autoimmune disorders, but also in patients with such diseases in order to clarify the degree to which the Treg cells might be functionally impaired [6,7].…”