Immune homeostasis enforced by co-localized effector and regulatory T cells

Zhiduo Liu, Michael Y. Gerner, Nicholas J. Van Panhuys, Andrew G. Levine, Alexander Y. Rudensky, Ronald N. Germain

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

FOXP3 + regulatory T cells (T reg cells) prevent autoimmunity by limiting the effector activity of T cells that have escaped thymic negative selection or peripheral inactivation. Despite the information available about molecular factors mediating the suppressive function of T reg cells, the relevant cellular events in intact tissues remain largely unexplored, and whether T reg cells prevent activation of self-specific T cells or primarily limit damage from such cells has not been determined. Here we use multiplex, quantitative imaging in mice to show that, within secondary lymphoid tissues, highly suppressive T reg cells expressing phosphorylated STAT5 exist in discrete clusters with rare IL-2-positive T cells that are activated by self-Antigens. This local IL-2 induction of STAT5 phosphorylation in T reg cells is part of a feedback circuit that limits further autoimmune responses. Inducible ablation of T cell receptor expression by T reg cells reduces their regulatory capacity and disrupts their localization in clusters, resulting in uncontrolled effector T cell responses. Our data thus reveal that autoreactive T cells are activated to cytokine production on a regular basis, with physically co-clustering T cell receptor-stimulated T reg cells responding in a negative feedback manner to suppress incipient autoimmunity and maintain immune homeostasis.

Original languageEnglish
Pages (from-to)225-230
Number of pages6
JournalNature
Volume528
Issue number7581
DOIs
Publication statusPublished - 10 Dec 2015
Externally publishedYes

Fingerprint

Regulatory T-Lymphocytes
Homeostasis
T-Lymphocytes
Autoimmunity
T-Cell Antigen Receptor
Interleukin-2
Autoantigens
Lymphoid Tissue
Cluster Analysis
Phosphorylation
Cytokines

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Liu, Z., Gerner, M. Y., Van Panhuys, N. J., Levine, A. G., Rudensky, A. Y., & Germain, R. N. (2015). Immune homeostasis enforced by co-localized effector and regulatory T cells. Nature, 528(7581), 225-230. https://doi.org/10.1038/nature16169

Immune homeostasis enforced by co-localized effector and regulatory T cells. / Liu, Zhiduo; Gerner, Michael Y.; Van Panhuys, Nicholas J.; Levine, Andrew G.; Rudensky, Alexander Y.; Germain, Ronald N.

In: Nature, Vol. 528, No. 7581, 10.12.2015, p. 225-230.

Research output: Contribution to journalArticle

Liu, Z, Gerner, MY, Van Panhuys, NJ, Levine, AG, Rudensky, AY & Germain, RN 2015, 'Immune homeostasis enforced by co-localized effector and regulatory T cells', Nature, vol. 528, no. 7581, pp. 225-230. https://doi.org/10.1038/nature16169
Liu Z, Gerner MY, Van Panhuys NJ, Levine AG, Rudensky AY, Germain RN. Immune homeostasis enforced by co-localized effector and regulatory T cells. Nature. 2015 Dec 10;528(7581):225-230. https://doi.org/10.1038/nature16169
Liu, Zhiduo ; Gerner, Michael Y. ; Van Panhuys, Nicholas J. ; Levine, Andrew G. ; Rudensky, Alexander Y. ; Germain, Ronald N. / Immune homeostasis enforced by co-localized effector and regulatory T cells. In: Nature. 2015 ; Vol. 528, No. 7581. pp. 225-230.
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