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PMID: 15235129 Published · ppublish English Journal Article

Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 28 ·2004-07-13 ·Pages 10398-403

Paust S, Lu L, McCarty N, Cantor H

Abstract

Although there is considerable evidence that a subpopulation of regulatory CD4(+)CD25+ T cells can suppress the response of autoreactive T cells, the underlying molecular mechanism is not understood. We find that transmission of a suppressive signal by CD4CD25+ regulatory cells requires engagement of the B7 molecule expressed on target T cells. The response of T cells from B7-deficient mice is resistant to suppression in vitro, and these cells provoke a lethal wasting disease in lymphopenic mice despite the presence of regulatory T cells. Susceptibility of B7-deficient cells to suppression is restored by lentiviral-based expression of full-length, but not truncated, B7 lacking a transmembrane/cytoplasmic domain. Because expression of these B7 truncation mutants restores CD28-dependent costimulatory activity, these findings that indicate B7-based transmission of suppressive activity suggest new approaches to modifying autoimmune responses.

MeSH Terms
Animals Autoimmune Diseases/immunology,prevention & control B7-1 Antigen/genetics,immunology,metabolism CD4-Positive T-Lymphocytes/immunology,transplantation DNA-Binding Proteins/genetics Gene Expression/immunology In Vitro Techniques Lymphopenia/immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Mutant Strains Retroviridae/genetics Signal Transduction/immunology Wasting Syndrome/immunology
Chemicals
B7-1 Antigen DNA-Binding Proteins Rag2 protein, mouse V(D)J recombination activating protein 2
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Paust Silke
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, 44 Binney Street, SM 722, Boston, MA 02115, USA.
Lu Linrong
McCarty Nami
Cantor Harvey
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0403342101
Published
2004-07-13
Epub
2004-00-02
Pages
10398-403
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC478583
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0403342101 PMC Full Text View journal details
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