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Interleukin-2 Fusion Protein (DAB389IL- 2) Selectively Targets Activated Human Peripheral Blood and Lamina Propria Lymphocytes

Digestive Diseases and Sciences volume 42, pages 1542–1548 (1997)Cite this article

Abstract

Activated mucosal T lymphocytes correlate withthe intestinal inflammation of inflammatory boweldisease. Activated T cells elaborate interferon-γ(IFN-γ) and express high-affinity interleukin-2(IL-2) receptors. The IL-2/diphtheria toxin fusionprotein (DAB389IL-2) has been shown tospecifically kill high affinity IL-2 receptor-bearingcells. We tested whether DAB389IL-2 couldspecifically target activated lamina propria lymphocytes. Lymphocytes 389were activated in vitro with phytohemagglutinin and IL-2for 24 - 48 hr. Toxin efficacy was determined by the[14C]leucine incorporation, IFN-γELISA, and flow cytometry. DAB389IL-2 (10-11 M) inhibited protein synthesis by 80% inactivated lamina propria 389 lymphocytes. Thisinhibition was blocked by coculture of either excessIL-2 or a nonfunctional IL-2 diphtheria toxin mutant protein.DAB389IL-2 (10-12 M) alsosignificantly reduced the numbers of activated helper Tcells and IFN-γ levels in 24-hr cultures.DAB389IL-2 specifically targets activatedIL-2 receptor-positive lamina propria lymphocytesand is a potential new therapeutic agent for patientswith active inflammatory bowel disease.

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Authors
  1. Athos Bousvaros
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  2. A. Christopher Stevens
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  3. Terry B. Strom
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  4. J. Murphy
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  5. J. Thomas Lamont
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Bousvaros, A., Stevens, A.C., Strom, T.B. et al. Interleukin-2 Fusion Protein (DAB389IL- 2) Selectively Targets Activated Human Peripheral Blood and Lamina Propria Lymphocytes. Dig Dis Sci 42, 1542–1548 (1997). https://doi.org/10.1023/A:1018891432581

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  • DOI: https://doi.org/10.1023/A:1018891432581

  • INTERLEUKIN-2
  • DIPHTHERIA TOXIN
  • LYMPHOCYTES
  • T CELLS
  • LAMINA PROPRIA