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PMID: 19136960 Published · ppublish English Journal Article Research Support, N.I.H., Intramural

Interleukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4+ T cells.

Nature immunology ·Vol. 10 ·No. 2 ·2009-02-00 ·Pages 149-57

Guimond M, Veenstra RG, Grindler DJ, Zhang H, Cui Y, Murphy RD, Kim SY, Na R, Hennighausen L, Kurtulus S, Erman B, Matzinger P, Merchant MS, Mackall CL

Abstract

Interleukin 7 (IL-7) and T cell antigen receptor signals have been proposed to be the main drivers of homeostatic T cell proliferation. However, it is not known why CD4(+) T cells undergo less-efficient homeostatic proliferation than CD8(+) T cells do. Here we show that systemic IL-7 concentrations increased during lymphopenia because of diminished use of IL-7 but that IL-7 signaling on IL-7 receptor-alpha-positive (IL-7Ralpha(+)) dendritic cells (DCs) in lymphopenic settings paradoxically diminished the homeostatic proliferation of CD4(+) T cells. This effect was mediated at least in part by IL-7-mediated downregulation of the expression of major histocompatibility complex class II on IL-7Ralpha(+) DCs. Our results indicate that IL-7Ralpha(+) DCs are regulators of the peripheral CD4(+) T cell niche and that IL-7 signals in DCs prevent uncontrolled CD4(+) T cell population expansion in vivo.

MeSH Terms
Animals CD4-Positive T-Lymphocytes/cytology,immunology,metabolism CD8-Positive T-Lymphocytes/cytology,immunology Cell Proliferation Dendritic Cells/immunology,metabolism Enzyme-Linked Immunosorbent Assay Feedback, Physiological Histocompatibility Antigens Class II/immunology,metabolism Homeostasis/immunology Interleukin-7/genetics,immunology,metabolism Lymphocyte Activation/immunology Lymphopenia/immunology,metabolism Mice Mice, Mutant Strains Receptors, Interleukin-7/immunology,metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction/physiology Stromal Cells/immunology,metabolism
Chemicals
Histocompatibility Antigens Class II Interleukin-7 Receptors, Interleukin-7
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Guimond Martin
Pediatric Oncology Branch, National Cancer Institute, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Veenstra Rachelle G
Grindler David J
Zhang Hua
Cui Yongzhi
Murphy Ryan D
Kim Su Young
Na Risu
Hennighausen Lothar
Kurtulus Sema
Erman Batu
Matzinger Polly
Merchant Melinda S
Mackall Crystal L
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1695
Published
2009-02-00
Epub
2009-00-11
Pages
149-57
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC2713006
Subset
IM
Grants
Intramural NIH HHS · Z01 SC010281-10 · United States
Corrections
CommentIn
PMID: 19148196
CommentIn
PMID: 20562832
External Links
PubMed source DOI: 10.1038/ni.1695 PMC Full Text View journal details
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