Immune homeostasis enforced by co-localized effector and regulatory T cells Journal Article
| Authors: | Liu, Z.; Gerner, M. Y.; Van, Panhuys, N.; Levine, A. G.; Rudensky, A. Y.; Germain, R. N. |
| Article Title: | Immune homeostasis enforced by co-localized effector and regulatory T cells |
| 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. |
| Keywords: | controlled study; protein phosphorylation; nonhuman; flow cytometry; transcription factor foxp3; animal cell; mouse; phenotype; mus; interleukin 2; dendritic cell; animal experiment; immunofluorescence; t lymphocyte receptor; regulatory t lymphocyte; cd4+ t lymphocyte; cellular distribution; cytokine production; effector cell; autoimmunity; feedback system; immunity; negative feedback; homeostasis; lymphoid tissue; stat5 protein; natural killer t cell; popliteal lymph node; priority journal; article |
| Journal Title: | Nature |
| Volume: | 528 |
| Issue: | 7581 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2015-12-10 |
| Start Page: | 225 |
| End Page: | 230 |
| Language: | English |
| DOI: | 10.1038/nature16169 |
| PROVIDER: | scopus |
| PMCID: | PMC4702500 |
| PUBMED: | 26605524 |
| DOI/URL: | |
| Notes: | Article -- 1 -- Export Date: 7 January 2016 -- 225 -- Source: Scopus |
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