Document Detail


CTLA4Ig prevents lymphoproliferation and fatal multiorgan tissue destruction in CTLA-4-deficient mice.
MedLine Citation:
PMID:  9164923     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mice lacking CTLA-4 develop a fatal spontaneous lymphoproliferative disease with massive lymphocytic infiltrates and tissue destruction in many organs. CTLA-4-deficient (-/-) splenocytes and lymph node cells proliferate without added stimuli in vitro. We report here that CTLA4Ig treatment of CTLA-4 -/- mice prevents lymphoproliferation and fatal multiorgan tissue damage in vivo and proliferation of CTLA-4 -/- splenocytes and lymph node cells in vitro. Therefore, stimulation via CD28-B7 interactions appears necessary for CTLA-4 -/- T cell proliferation and the production of lymphoproliferative disease in vivo. When CTLA4Ig treatment is terminated, CTLA-4 -/- T cells become activated and lymphoproliferative disease develops. The lack of long term protective effects of CTLA4Ig treatment suggests that CTLA-4 is needed for the induction and or maintenance of tolerance.
Authors:
E A Tivol; S D Boyd; S McKeon; F Borriello; P Nickerson; T B Strom; A H Sharpe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  158     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1997 Jun 
Date Detail:
Created Date:  1997-06-19     Completed Date:  1997-06-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  5091-4     Citation Subset:  AIM; IM    
Affiliation:
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD
Antigens, Differentiation / administration & dosage,  genetics,  immunology*
Cell Division / drug effects
Immune Tolerance / genetics,  immunology
Immunoconjugates*
Immunosuppressive Agents / administration & dosage
Lymphoproliferative Disorders / genetics,  immunology*,  pathology,  prevention & control
Mice
Mice, Knockout
Grant Support
ID/Acronym/Agency:
1P30AR42689/AR/NIAMS NIH HHS; P01 AI35225/AI/NIAID NIH HHS; T32 HLO7627/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, Differentiation; 0/Immunoconjugates; 0/Immunosuppressive Agents; 0/abatacept; 0/cytotoxic T-lymphocyte antigen 4

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