Continuous Activation of Autoreactive CD4+ CD25+ Regulatory T Cells in the Steady State

By S. Fisson, G. Darrasse-Jéze, E. Litvinova, Franck Septier, David Klatzmann, R. Liblau, B. Salomon. Journal of Experimental Medicine, 2003

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Despite a growing interest in CD4+ CD25+ regulatory T cells (Treg) that play a major role in self-tolerance and immunoregulation, fundamental parameters of the biology and homeostasis of these cells are poorly known. Here, we show that this population is composed of two Treg subsets that have distinct phenotypes and homeostasis in normal unmanipulated mice. In the steady state, some Treg remain quiescent and have a long lifespan, in the order of months, whereas the other Treg are dividing extensively and express multiple activation markers. After adoptive transfer, tissue-specific Treg rapidly divide and expand preferentially in lymph nodes draining their target self-antigens. These results reveal the existence of a cycling Treg subset composed of autoreactive Treg that are continuously activated by tissue self-antigens.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/dcaafca9987b01d148766d59c7880c4a4b62db99

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Citations in the corpus

Deacetylase inhibition promotes the generation and function of regulatory T cells (2007, background): “Naturally occurring T reg cells arise during thymic development and enter the periphery, surviving for 70 d or mor”
Regulatory T Cells and Human Disease. (2020, background): “FoxP3+ Tregs, especially effector type Tregs, are continuously in a highly proliferative state in the normal physiological state, presumably due to recognizing self-antigens and antigens derived from commensal microbes (39, 40).”
FOXP3+ regulatory T cells in the human immune system (2010, background): “However, based on mouse data, T Reg cells need to be stimulated continuously by their cognate antigen, presumably self antigen, to be maintained in the peripher”
Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke (2009, background): “Early suppression of TNF-α and IL-1β release as well as a reduction in microglial activation in the presence of steady-state T reg cells are probably due to the continuous activation of a large part of autoreactive T reg cell”
Foxp3 Expressing CD4+CD25high Regulatory T Cells Are Overrepresented in Human Metastatic Melanoma Lymph Nodes and Inhibit the Function of Infiltrating T Cells1 (2004, background): “(46) that in mice, a fraction of Treg present in normal LNs and spleen is continuously activated and is dividing in the steady-state while another fraction remains quiescent.”
Regulatory T cells and immune tolerance. (2008, background): “Notably, unlike their hypoproliferation upon antigenic stimulation in vitro, a sizable fraction of Foxp3 + natural Tregs are continuously proliferating in vivo presumably through the recognition of selfantigen and commensal microbes (Fisson et al., 2003; Setoguchi et al., 2005).”
Foxp3+CD25+CD4+ natural regulatory T cells in dominant self‐tolerance and autoimmune disease (2006, background): “At least some of them are in a more proliferative state than other T cells in the periphery of normal animals, presumably because of the strong recognition of normal self-antigens (13).”