Regulatory T Cells

Regulatory T cells are a subset of T cells which modulate the immune system and keep immune reactions in check.

Learning Objective

Describe the function and types of regulatory T cells

Key Points

Regulatory T cells (Tregs) are critical to the maintenance of immune cell homeostasis as evidenced by the consequences of genetic or physical ablation of the Treg population.
Tregs are classified into natural or 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-2R alpha) expression outside of the thymus and are typically induced by inflammation and disease processes, such as autoimmunity and cancer.

Term

autoimmunity
The condition where one's immune system attacks one's own tissues, i.e., an autoimmune disorder.

Full Text

Regulatory T cells are a component of the immune system that suppress immune responses of other cells. This is an important "self-check" built into the immune system to prevent excessive reactions and chronic inflammation. Regulatory T cells come in many forms, with the most well-understood being those that express CD4, CD25 , and Foxp3. These cells are also called CD4⁺CD25⁺ regulatory T cells, or Tregs. These cells are involved in shutting down immune responses after they have successfully eliminated invading organisms, and also in preventing autoimmunity.

CD25 is a component of the IL2 receptor

Interleukin 2 receptor is composed of three subunits (alpha, beta, and gamma). CD25 constitutes the alpha chain of the IL2 receptor.

CD4⁺Foxp3⁺ regulatory T cells have been called "naturally-occurring" regulatory T cells, to distinguish them from "suppressor" T cell populations that are generated in vitro. Additional suppressor T cell populations include Tr1, Th3, CD8⁺CD28^-, and Qa-1 restricted T cells. The contribution of these populations to self-tolerance and immune homeostasis is less well defined. FOXP3 can be used as a good marker for CD4+CD25+ T cells as well as recent studies showing evidence for FOXP3 in CD4+CD25- T cells.

An additional regulatory T cell subset, induced regulatory T cells, are also needed for tolerance and suppression. Induced Regulatory T (iTreg) cells (CD4⁺CD25⁺Foxp3⁺) are suppressive cells involved in tolerance. iTreg cells have been shown to suppress T cell proliferation and experimental autoimmune diseases. iTreg cells develop from mature CD4⁺ conventional T cells outside of the thymus: a defining distinction between natural regulatory T (nTreg) cells and iTreg cells. Though iTreg and nTreg cells share a similar function iTreg cells have recently been shown to be an essential non-redundant regulatory subset that supplements nTreg cells, in part by expanding TCR diversity within regulatory responses. Acute depletion of the iTreg cell pool in mouse models has resulted in inflammation and weight loss. The contribution of nTreg cells versus iTreg cells in maintaining tolerance is unknown, but both are important. Epigenetic differences have been observed between nTreg and iTreg cells, with the former having more stable Foxp3 expression and wider demethylation.

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