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PMID: 14976053 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Induction of antigen-specific tolerance to bone marrow allografts with CD4+CD25+ T lymphocytes.

Blood ·Vol. 103 ·No. 11 ·2004-06-01 ·Pages 4216-21

Joffre O, Gorsse N, Romagnoli P, Hudrisier D, van Meerwijk JP

Abstract

Thymus-derived regulatory T lymphocytes of CD4(+)CD25(+) phenotype regulate a large variety of beneficial and deleterious immune responses and can inhibit lethal graft-versus-host disease in rodents. In vitro, CD4(+)CD25(+) T cells require specific major histocompatibility complex (MHC)/peptide ligands for their activation, but once activated they act in an antigen-nonspecific manner. In vivo, regulatory T cells are also activated in an antigen-specific fashion, but nothing is known about antigen specificity of their suppressor-effector function. Here we show that CD4(+)CD25(+) regulatory T lymphocytes isolated from naive mice and activated in vitro with allogeneic antigen-presenting cells (APCs) induced specific long-term tolerance to bone marrow grafts disparate for major and minor histocompatibility antigens; whereas "target" bone marrow was protected, third-party bone marrow was rejected. Importantly, in mice injected with a mix of target and third-party bone marrows, protection and rejection processes took place simultaneously. These results indicate that CD4(+)CD25(+) regulatory T cells can act in an antigen-specific manner in vivo. Our results suggest that CD4(+)CD25(+) regulatory T cells could in the future be used in clinical settings to induce specific immunosuppression.

MeSH Terms
Animals Bone Marrow Cells/immunology Bone Marrow Transplantation/immunology CD4-Positive T-Lymphocytes/chemistry,cytology,immunology CD8-Positive T-Lymphocytes/cytology,immunology Cells, Cultured Epitopes Graft Rejection/immunology Haplotypes Histocompatibility Antigens/genetics Immune Tolerance/immunology Mice Mice, Inbred C57BL Mice, Inbred DBA Receptors, Interleukin-2/analysis Spleen/cytology,immunology Transplantation, Homologous
Chemicals
Epitopes Histocompatibility Antigens Receptors, Interleukin-2
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Joffre Olivier
Tolerance and Autoimmunity Section, Institut National de la Santé et de la Recherche Médicale, Centre de Physiopathologie de Toulouse Purpan, Institut de Preval, France.
Gorsse Nathalie
Romagnoli Paola
Hudrisier Denis
van Meerwijk Joost P M
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2004-01-0005
Published
2004-06-01
Epub
2004-00-19
Pages
4216-21
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC2516529
Subset
IM
External Links
PubMed source DOI: 10.1182/blood-2004-01-0005 PMC Full Text View journal details
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