Document Detail

Intravenous apoptotic spleen cell infusion induces a TGF-beta-dependent regulatory T-cell expansion.
MedLine Citation:
PMID:  15962005     Owner:  NLM     Status:  MEDLINE    
Apoptotic leukocytes are endowed with immunomodulatory properties that can be used to enhance hematopoietic engraftment and prevent graft-versus-host disease (GvHD). This apoptotic cell-induced tolerogenic effect is mediated by host macrophages and not recipient dendritic cells or donor phagocytes present in the bone marrow graft as evidenced by selective cell depletion and trafficking experiments. Furthermore, apoptotic cell infusion is associated with TGF-beta-dependent donor CD4+CD25+ T-cell expansion. Such cells have a regulatory phenotype (CD62L(high) and intracellular CTLA-4+), express high levels of forkhead-box transcription factor p3 (Foxp3) mRNA and exert ex vivo suppressive activity through a cell-to-cell contact mechanism. In vivo CD25 depletion after apoptotic cell infusion prevents the apoptotic cell-induced beneficial effects on engraftment and GvHD occurrence. This highlights the role of regulatory T cells in the tolerogenic effect of apoptotic cell infusion. This novel association between apoptosis and regulatory T-cell expansion may also contribute to preventing deleterious autoimmune responses during normal turnover.
F Kleinclauss; S Perruche; E Masson; M de Carvalho Bittencourt; S Biichle; J-P Remy-Martin; C Ferrand; M Martin; H Bittard; J-M Chalopin; E Seilles; P Tiberghien; P Saas
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell death and differentiation     Volume:  13     ISSN:  1350-9047     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-12-12     Completed Date:  2006-03-20     Revised Date:  2013-03-21    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  41-52     Citation Subset:  IM    
INSERM U645, 1 Bd A Fleming, Besançon F-25020, France.
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MeSH Terms
Adoptive Transfer
Apoptosis / immunology*
Bone Marrow Transplantation / immunology
Dendritic Cells / immunology
Forkhead Transcription Factors / genetics
Graft Survival / immunology
Graft vs Host Disease / prevention & control
Immune Tolerance
Macrophages / immunology
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
RNA, Messenger / genetics
Receptors, Interleukin-2 / metabolism
Spleen / cytology*,  immunology*
T-Lymphocytes, Regulatory / immunology*
Transforming Growth Factor beta / metabolism*
Reg. No./Substance:
0/Forkhead Transcription Factors; 0/Foxp3 protein, mouse; 0/RNA, Messenger; 0/Receptors, Interleukin-2; 0/Transforming Growth Factor beta

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