Regulators of the Immune System

Regulatory T cells (Tregs) are critical to the maintenance of immune cell homeostasis as evidenced by the catastrophic consequences of genetic or physical ablation of the Treg population. Specifically, Treg cells maintain order in the immune system by enforcing a dominant negative regulation on other immune cells. Broadly classified into natural or adaptive (induced) Tregs; natural Tregs are CD4+CD25+ T-cells which develop, and emigrate from the thymus to perform their key role in immune homeostasis. Adaptive Tregs are non-regulatory CD4+ T-cells which acquire CD25 (IL-2Rα) expression outside of the thymus, and are typically induced by inflammation and disease processes, such as autoimmunity and cancer.

Precise understanding of the immunosuppressive mechanism of Treg cells remains elusive, although there is increasing evidence that Tregs manifest their function through a myriad of mechanisms that include the secretion of immunosuppressive soluble factors such as IL-9, IL-10 and TGFβ, cell contact mediated regulation via the high affinity TCR and other costimulatory molecules such as CTLA-4, GITR, and cytolytic activity. Understanding the mechanisms by which Treg cells exert their influence is an area of intense research with broad implications for the development of therapeutic strategies for many disease processes including cancer, diabetes, and Immune mediated diseases.

Under the influence of TGF-ß adaptive Treg cells mature in peripheral sites, including mucosa-associated lymphoid tissue (MALT), from CD4+ Treg precursors, where they acquire the expression of markers typical of Tregs, including CD25, CTLA4 and GITR/AITR. Upon up-regulation of the transcription factor Foxp3, Treg cells begin their suppressive effect. This includes the secretion of cytokines including IL-10 and TGFß which may induce cell-cycle arrest or apoptosis in effector T cells, and blocking co-stimulation and maturation of dendritic cells.

Properties of Tregs
Property	Natural Treg (nTreg)	Induced Treg (iTreg) - Tr1	Induced Treg (iTreg) - Th3
Development	Thymus	Periphery (MALT)	Periphery (MALT)
Phenotype	CD4⁺CD25⁺CD127^low	CD4⁺CD25^-	CD4⁺CD25⁺ from CD25^- precursors
Other Associated Markers	CTLA-4⁺GITR⁺Foxp3⁺	CD45RB^lowFoxp3^-	CD25^low-variableCD45RB^lowFoxp3⁺
Suppression	Contact-, Granzyme B-dependent, makes TGFβ	IL-10-mediated	TGFβ-mediated
Target Cells	APC and Effector T Cells	Effector T Cells	Unknown
CD28 Involvement	Thymic development and maintenance in periphery	Unnecessary for development or function	Unnecessary for development or function
In vivo Role	Suppression of autoreactive T cells	Mucosal immunity, inflammatory response	Mucosal immunity, inflammatory response
In vitro Expansion	TCR/CD28 stimulation and IL-2	CD3, IL-10, Retinoic Acid	CD3, TGFβ

eBioscience Provides a Complete Solution for Treg Analysis

eBioscience is proud to lead the way in providing novel reagents for the complete analysis of this important T cell lineage. Since our introduction of the first Foxp3 antibody for the identification of Treg cells by flow cytometry, eBioscience has continued to release new reagents to further characterization of the Treg lineage allowing researchers to make significant progress in understanding disease.

NEW Treg Products from eBioscience

Mouse Treg Cells
Human Treg Cells

References

Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Takahashi T, Kuniyasu Y, Toda M, Sakaguchi N, Itoh M, Iwata M, Shimizu J, Sakaguchi S. Int Immunol. 1998 Dec;10(12):1969-80.

Regulatory T cells in autoimmmunity. Shevach EM. Annu Rev Immunol. 2000;18:423-49. Review.

Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor? Curotto de Lafaille MA, Lafaille JJ. Immunity. 2009 May;30(5):626-35. Review.