Naturally occurring regulatory T cells: markers, mechanisms, and manipulation

Abstract

Naturally occurring CD4(+)CD25(high) forkhead box protein 3 (FOXP3)(+) regulatory T cells (nTregs) are key mediators of immunity, which orchestrate and maintain tolerance to self and foreign antigens. In the recent 1.5 decades, a multitude of studies have aimed to define the phenotype and function of nTregs and to assess their therapeutic potential for modulating immune mediated disorders such as autoimmunity, allergy, and episodes of transplant rejection. In this review, we summarize the current knowledge on the biology of nTregs. We address the exact definition of nTregs by specific markers and combinations thereof, which is a prerequisite for the state-of-the-art isolation of defined nTreg populations. Furthermore, we discuss the mechanism by which nTregs mediate immunosuppression and how this knowledge might translate into novel therapeutic modalities. With first clinical studies of nTreg-based therapies being finished, questions concerning the reliable sources of nTregs are becoming more and more eminent. Consequently, approaches allowing conversion of CD4(+) T cells into nTregs by coculture with antigen-presenting cells, cytokines, and/or pharmacological agents are discussed. In addition, genetic engineering approaches for the generation of antigen-specific nTregs are described.

Helios+ and Helios− Cells Coexist within the Natural FOXP3+ T Regulatory Cell Subset in Humans

“…Human nTregs cells can be divided into many subsets on the basis of a variety of cell surface molecules such as HLA-DR, GITR, and ICOS (35), as well as transcription factors such as T-BET (34). In this study, we show that nTregs can also be divided on the basis of Helios expression.…”

Eosinophil Granule Proteins: Form and Function

“…1). EPX and MBP-2 are the only EDGPs uniquely expressed by the eosinophil and not other cells; the other EDGPs are variably expressed in ϳ10 -100-fold lesser amounts by other blood leukocytes, tissues, and cells including basophils (MBP-1 (14,15), EDN (16), CLC/Gal-10 (17, 18)), neutrophils (EDN, ECP) (19 -21), liver (EDN) (22), and regulatory T cells (Tregs) (23,24) and T H 2 central memory T cells (CLC/Gal-10) (25). Although these EDGPs are expressed and may be secreted by these other cell types at sites of host innate and adaptive immune responses and inflammation, aside from expression of CLC/Gal-10 by regulatory T cells (23), the roles and functions of these proteins beyond those of eosinophils have not been investigated, other than their potential use as biomarkers.…”

Years in Review: Recent Progress in Cellular Allergology

“…Different subsets of naturally occurring Treg cells have been defined and reviewed recently [35]. They express the coreceptor CD4, high levels of the high-affinity IL-2 receptor, CD25, and are positive for the transcription factor FoxP3 [36].…”