Development and function of naturally occurring CD4+CD25+ regulatory T cells

Abstract

The immune system has evolved numerous mechanisms of peripheral T cell immunoregulation, including a network of regulatory T (Treg) cells, to modulate and down-regulate immune responses at various times and locations and in various inflammatory circumstances. Amongst these, naturally occurring CD4(+)CD25(+) Treg cells (nTreg) represent a major lymphocyte population engaged in the dominant control of self-reactive T responses and maintaining tolerance in several models of autoimmunity. CD4(+)CD25(+) Treg cells differentiate in the normal thymus as a functionally distinct subpopulation of T cells bearing a broad T cell receptor repertoire, endowing these cells with the capacity to recognize a wide range of self and nonself antigen specificities. The generation of CD4(+)CD25(+) Treg cells in the immune system is genetically controlled, influenced by antigen recognition, and various signals, in particular, cytokines such as interleukin-2 and transforming growth factor-beta1, control their activation, expansion, and suppressive effector activity. Functional abrogation of these cells in vivo or genetic defects that affect their development or function unequivocally promote the development of autoimmune and other inflammatory diseases in animals and humans. Recent progress has shed light on our understanding of the cellular and molecular basis of CD4(+)CD25(+) Treg cell-mediated immune regulation. This article discusses the relative contribution of CD4(+)CD25(+) nTreg cells in the induction of immunologic self-tolerance and provides a comprehensive overview of recent finding regarding the functional properties and effector mechanism of these cells, as revealed from various in vitro and in vivo models.

Immune responses to adeno-associated virus type 2 encoding channelrhodopsin-2 in a genetically blind rat model for gene therapy

“…38,39 CD25, an interleukin-2 receptor, is reported to be an inflammation marker on CD4 + lymphocytes. 18 In the EIU experiment, we observed expansion of CD4 + CD25 + cells, which is consistent with the report by Toda et al 19 A significant increase in the number of CD4 + CD25 + cells was observed in both the rAAV-Venus and the rAAV-ChR2V rats at 1 week after the injections compared with the pre-injection values (Figure 8b), although there was no significant difference in the results between the rAAV-Venus and the rAAV-ChR2V injections. …”

“…There was no significant difference in the inflammation status between the rAAV injections. As a positive control of inflammation, EIU also increased the population of CD4 + CD25 + cells, which is consistent with a report by Toda et al 19 …”

T Regulatory Cells Control Numbers of NK Cells and CD8α+ Immature Dendritic Cells in the Lymph Node Paracortex

“…It is generally viewed that Treg cells interact with other cells through cell-cell contact or short-range interactions to mediate their effects (23)(24)(25). To explain discrepancies (in the number of NK cells and function of NK precursors) between the spleen and LNs, we therefore evaluated the propitiousness of the environments of the LN and the spleen to short-range interactions between Treg cells and NK lineage cells.…”

The IL-2/CD25 Pathway Determines Susceptibility to T1D in Humans and NOD Mice

“…CD25 is constitutively expressed at high levels on CD4 + Foxp3 + regulatory T cells (Tregs), which suppress putatively autoreactive peripheral T cells that escape thymic deletion during the establishment of central tolerance [74][75][76][77], and Treg depletion causes autoimmunity in mouse models [78]. Foxp3 is a transcription factor that is fundamental for Treg production and function [79][80][81]: Targeted ablation of the Foxp3 gene results in severe autoimmune manifestations in mice, and in humans, natural mutations of the orthologous gene lead to immune dysregulation, polyendocrinopathy, enteropathy, and Xlinked inheritance (IPEX) syndrome [82][83][84] and X-linked autoimmunity-allergic dysregulation syndrome [85].…”