Document Detail

Interleukin-2 fusion protein with anti-CD3 single-chain Fv (sFv) selectively protects T cells from dexamethasone-induced apoptosis.
MedLine Citation:
PMID:  11672928     Owner:  NLM     Status:  MEDLINE    
Apoptosis of mature T cells may be an important pathophysiologic mechanism in diseases such as AIDS, cancer, and autoimmunity. In this study, in order to selectively protect T cells from dexamethasone (DEX)-induced apoptosis we constructed a fusion protein (anti-CD3sFv-IL-2) in which anti-CD3 single-chain Fv (sFv), the smallest unit of antibody recognizing the CD3 epsilon moiety of the T-cell receptor (TCR), was covalently linked to murine interleukin-2 (IL-2). Recombinant anti-CD3sFv protein was also expressed and used as a control. The purified anti-CD3sFv-IL-2 protein displayed IL-2 bioactivity in an IL-2 proliferation assay, which was inhibited by a neutralizing mIL-2 mAb. The anti-CD3sFv-IL-2 protein protected T lymphoma cells (S49.1) from DEX-induced apoptosis as demonstrated by oligonucleosomal genomic DNA fragmentation assay, and also recovered proliferation capacity of DEX-treated S49.1 cells and increased T cell composition both in DEX-treated spleen cell-populations and in DEX-treated mice, while the anti-CD3sFv protein did not. In addition, the anti-CD3sFv-IL-2 fusion protein was more efficient than a simple mixture of anti-CD3sFv and free rIL-2 in selectively protecting T cells from DEX-induced apoptosis. The levels of bcl-2 gene expression were significantly increased in DEX-treated T cells in the presence of the anti-CD3sFv-IL-2 protein. These studies indicate that the anti-CD3sFv-IL-2 fusion protein can selectively protect T cells from DEX-induced apoptosis and that the covalent linkage of anti-CD3sFv and IL-2 confines the anti-apoptotic effect of IL-2 to T cells.
E J Kim; D Cho; S Y Hwang; T S Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Vaccine     Volume:  20     ISSN:  0264-410X     ISO Abbreviation:  Vaccine     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-10-23     Completed Date:  2002-01-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8406899     Medline TA:  Vaccine     Country:  England    
Other Details:
Languages:  eng     Pagination:  608-15     Citation Subset:  IM    
College of Pharmacy, Chonnam National University, Kwangju 500-757, South Korea.
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MeSH Terms
Antigens, CD3 / immunology*
Apoptosis / drug effects*
Dexamethasone / pharmacology*
Genes, bcl-2
Immunoglobulin Fragments / pharmacology*
Interleukin-2 / pharmacology*
Lymphocyte Activation / drug effects
Mice, Inbred C57BL
Recombinant Fusion Proteins / pharmacology*
T-Lymphocytes / cytology,  drug effects*
Reg. No./Substance:
0/Antigens, CD3; 0/Immunoglobulin Fragments; 0/Interleukin-2; 0/Recombinant Fusion Proteins; 0/immunoglobulin Fv; 50-02-2/Dexamethasone

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