Hypothesis & Theory ARTICLE

Front. Immunol., 25 May 2012 | doi: 10.3389/fimmu.2012.00125

Quorum-sensing in CD4+ T cell homeostasis: a hypothesis and a model

Afonso R. M. Almeida1, Inês F. Amado2,3,4, Joseph Reynolds5, Julien Berges2,3,6, Grant Lythe5, Carmen Molina-París5 and Antonio A. Freitas2,3*
  • 1 Immunobiology Unit, Institute for Molecular Medicine, Lisboa, Portugal
  • 2 Institut Pasteur, Département d’Immunologie, Unité de Biologie des Populations Lymphocytaires, Paris, France
  • 3 CNRS, URA1961, Paris, France
  • 4 GABBA, ICBAS, Universidade do Porto, Porto, Portugal
  • 5 Department of Applied Mathematics, School of Mathematics, University of Leeds, Leeds, UK
  • 6 Université Pierre et Marie Curie, Cellule Pasteur UPMC, Paris, France

Homeostasis of lymphocyte numbers is believed to be due to competition between cellular populations for a common niche of restricted size, defined by the combination of interactions and trophic factors required for cell survival. Here we propose a new mechanism: homeostasis of lymphocyte numbers could also be achieved by the ability of lymphocytes to perceive the density of their own populations. Such a mechanism would be reminiscent of the primordial quorum-sensing systems used by bacteria, in which some bacteria sense the accumulation of bacterial metabolites secreted by other elements of the population, allowing them to “count” the number of cells present and adapt their growth accordingly. We propose that homeostasis of CD4+ T cell numbers may occur via a quorum-sensing-like mechanism, where IL-2 is produced by activated CD4+ T cells and sensed by a population of CD4+ Treg cells that expresses the high-affinity IL-2Rα-chain and can regulate the number of activated IL-2-producing CD4+ T cells and the total CD4+ T cell population. In other words, CD4+ T cell populations can restrain their growth by monitoring the number of activated cells, thus preventing uncontrolled lymphocyte proliferation during immune responses. We hypothesize that malfunction of this quorum-sensing mechanism may lead to uncontrolled T cell activation and autoimmunity. Finally, we present a mathematical model that describes the key role of IL-2 and quorum-sensing mechanisms in CD4+ T cell homeostasis during an immune response.

Keywords: CD4+ T cells, regulatory T cells, IL-2, autoimmunity, immune-therapy, homeostasis, quorum sensing, mathematical modeling

Citation: Almeida ARM, Amado IF, Reynolds J, Berges J, Lythe G, Molina-París C and Freitas AA (2012) Quorum-sensing in CD4+ T cell homeostasis: a hypothesis and a model. Front. Immun. 3:125. doi: 10.3389/fimmu.2012.00125

Afonso R. M. Almeida and Inês F. Amado are the first co-authors.

Received: 13 March 2012; Paper pending published: 06 April 2012;
Accepted: 02 May 2012; Published online: 25 May 2012.

Edited by:

Kendall A. Smith, Weill Medical College of Cornell University, USA

Reviewed by:

Kendall A. Smith, Weill Medical College of Cornell University, USA
Shohei Hori, RIKEN, Japan

Copyright: © 2012 Almeida, Amado, Reynolds, Berges, Lythe, Molina-París and Freitas. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

*Correspondence: Antonio A. Freitas, Institut Pasteur, Département d’Immunologie, Unité de Biologie des Populations Lymphocytaires, 25, rue du Dr. Roux, 75015 Paris, France. e-mail: antonio.freitas@pasteur.fr

Afonso R. M. Almeida and Inês F. Amado are the first co-authors.

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