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Review
. 2009 Oct;70(4):326-36.
doi: 10.1111/j.1365-3083.2009.02308.x.

How do regulatory T cells work?

A Corthay  1
Affiliations
Free PMC article
Review

How do regulatory T cells work?

A Corthay. Scand J Immunol. 2009 Oct.
Free PMC article

Abstract

CD4(+) T cells are commonly divided into regulatory T (Treg) cells and conventional T helper (Th) cells. Th cells control adaptive immunity against pathogens and cancer by activating other effector immune cells. Treg cells are defined as CD4(+) T cells in charge of suppressing potentially deleterious activities of Th cells. This review briefly summarizes the current knowledge in the Treg field and defines some key questions that remain to be answered. Suggested functions for Treg cells include: prevention of autoimmune diseases by maintaining self-tolerance; suppression of allergy, asthma and pathogen-induced immunopathology; feto-maternal tolerance; and oral tolerance. Identification of Treg cells remains problematic, because accumulating evidence suggests that all the presently-used Treg markers (CD25, CTLA-4, GITR, LAG-3, CD127 and Foxp3) represent general T-cell activation markers, rather than being truly Treg-specific. Treg-cell activation is antigen-specific, which implies that suppressive activities of Treg cells are antigen-dependent. It has been proposed that Treg cells would be self-reactive, but extensive TCR repertoire analysis suggests that self-reactivity may be the exception rather than the rule. The classification of Treg cells as a separate lineage remains controversial because the ability to suppress is not an exclusive Treg property. Suppressive activities attributed to Treg cells may in reality, at least in some experimental settings, be exerted by conventional Th cell subsets, such as Th1, Th2, Th17 and T follicular (Tfh) cells. Recent reports have also demonstrated that Foxp3(+) Treg cells may differentiate in vivo into conventional effector Th cells, with or without concomitant downregulation of Foxp3.

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Figures

Figure 1
Figure 1
Five key questions about Treg cells. (A) What are the functions of Treg cells? (B) What molecular markers can be used to distinguish Treg cells from conventional Th cells? (C) Do Treg cells recognize self or non-self? (D) Do Treg cells represent a distinct lineage of CD4+ T cells? (E) How do Treg cells know which Th cell to suppress? In other words, how do Treg cells discriminate between the bad (i.e. self-reactive) Th cells, which should be suppressed, and the good (i.e. virus-specific) Th cells which should not?
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