Regulatory T Cells Selectively Express Toll-like Receptors and Are Activated by Lipopolysaccharide

By Í. Caramalho, Thiago Lopes-Carvalho, D. Ostler, S. Zelenay, M. Haury, J. Demengeot. Journal of Experimental Medicine, 2003

1,091 citations recorded by the source corpus.

Regulatory CD4 T cells (Treg) control inflammatory reactions to commensal bacteria and opportunist pathogens. Activation of Treg functions during these processes might be mediated by host-derived proinflammatory molecules or directly by bacterial products. We tested the hypothesis that engagement of germline-encoded receptors expressed by Treg participate in the triggering of their function. We report that the subset of CD4 cells known to exert regulatory functions in vivo (CD45RBlow CD25+) selectively express Toll-like receptors (TLR)-4, -5, -7, and -8. Exposure of CD4+ CD25+ cells to the TLR-4 ligand lipopolysaccharide (LPS) induces up-regulation of several activation markers and enhances their survival/proliferation. This proliferative response does not require antigen-presenting cells and is augmented by T cell receptor triggering and interleukin 2 stimulation. Most importantly, LPS treatment increases CD4+ CD25+ cell suppressor efficiency by 10-fold and reveals suppressive activity in the CD4+ CD45RBlow CD25− subset that when tested ex-vivo, scores negative. Moreover, LPS-activated Treg efficiently control naive CD4 T cell–dependent wasting disease. These findings provide the first evidence that Treg respond directly to proinflammatory bacterial products, a mechanism that likely contributes to the control of inflammatory responses.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/1fa13f1a2fa5dce7eba855719655e5cb09adbf5e

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In Immunology

1. D. Munn
2. A. Mellor
3. V. Kuchroo
4. Shimon Sakaguchi
5. K. Mills
6. B. Blazar
7. David Klatzmann
8. H. Yagita

Citations in the corpus

• Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. (2007, background): “Tregs isolated from TDLNs in vivo were constitutively activated, displaying spontaneous suppressor activity that was as potent as the highest levels reported for Tregs extensively activated in vitro (15, 16).”
• Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses (2009, background): “TLRs may also play a role in mechanisms of immune suppression by regulatory T lymphocytes and in humoral immune responses mediated by B lymphocytes (48, 289, 290).”
• Toll-like receptors in the pathogenesis of human disease (2004, background): “Alternatively, the D299G polymorphism may affect the function of CD4 + CD25 + regulatory T cells, which not only express TLR4 but also are activated by LP”
• Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. (2004, background): “[69] Caramalho I, Lopes-Carvalho T, Ostler D, Zelenay S, Haury M, De-”
• Cytokines in atherosclerosis: pathogenic and regulatory pathways. (2006, background): “Remarkably, CD4 CD25 Treg cells selectively express TLR4–5-7–8 (110).”
• Continuous Activation of Autoreactive CD4+ CD25+ Regulatory T Cells in the Steady State (2003, background): “In vitro data showed that Treg do not proliferate to antigenic or anti-CD3 stimulation, except if IL-2, anti-CD28 antibody, or lipopolysaccharide is added to the culture (43, 44, 48).”
• Regulatory T cells: friend or foe in immunity to infection? (2004, background): “Finally, it has also been proposed that regulatory T cells might respond directly to physiological or pathogenic ligand interaction with TLR4 (Ref”
• Tim-3 inhibits T helper type 1–mediated auto- and alloimmune responses and promotes immunological tolerance (2003, result): “This last interpretation would be consistent with observations concerning the function of dendritic cell phenotype in the modulation of CD4 + CD25 + T cell–mediated immunoregulatio”
• Modulation of tryptophan catabolism by regulatory T cells (2003, background): “These treatments have been reported to enhance the suppressive potential of T R cell”
• Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self (2005, background): “In addition, natural CD25 + CD4 + T reg cells are reported to selectively express several members of the TLR family, such as TLR4 (ref”