Interleukin-2 fusion protein with anti-CD3 single-chain Fv (sFv) selectively protects T cells from dexamethasone-induced apoptosis

Eui J. Kim, Dae Ho Cho, Seung Y. Hwang, Tae Sung Kim

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)608-615
Number of pages8
JournalVaccine
Volume20
Issue number3-4
DOIs
Publication statusPublished - 2001 Nov 12
Externally publishedYes

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Keywords

  • Anti-CD3
  • Apoptosis
  • Fusion vaccine
  • Interleukin-2
  • T cell

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)

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