Skip to main content
Journal cover image

A new nucleic acid-based agent inhibits cytotoxic T lymphocyte-mediated immune disorders.

Publication ,  Journal Article
Wang, C-W; Chung, W-H; Cheng, Y-F; Ying, N-W; Peck, K; Chen, Y-T; Hung, S-I
Published in: J Allergy Clin Immunol
September 2013

BACKGROUND: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and graft-versus-host disease (GVHD) are distinct immune reactions elicited by drugs or allogeneic antigens; however, they share a pathomechanism with the activation of cytotoxic T lymphocytes (CTLs). CTLs produce cytotoxic proteins, cytokines, chemokines, or immune alarmins, such as granulysin (GNLY), leading to the extensive tissue damage and systemic inflammation seen in patients with SJS/TEN or GVHD. Currently, there is no effective therapeutic agent specific for CTL-mediated immune disorders. OBJECTIVES: By targeting GNLY(+) CTLs, we aimed to develop a nucleic acid-based agent consisting of an anti-CD8 aptamer with GNLY small interfering RNA (siRNA). METHODS: We performed systematic evolution of ligands using exponential enrichment to select and identify effective anti-CD8 aptamers. We developed an aptamer-siRNA chimera using a "sticky bridge" method by conjugating the aptamer with siRNA. We analyzed the inhibitory effects of the aptamer-siRNA chimera on CTL responses in patients with SJS/TEN or GVHD. RESULTS: We identified a novel DNA aptamer (CD8AP17s) targeting CTLs. This aptamer could be specifically internalized into human CTLs. We generated the CD8AP17s aptamer-GNLY siRNA chimera, which showed a greater than 79% inhibitory effect on the production of GNLY by drug/alloantigen-activated T cells. The CD8AP17s aptamer-GNLY siRNA chimera decreased cytotoxicity in in vitro models of both SJS/TEN (elicited by drug-specific antigen) and GVHD (elicited by allogeneic antigens). CONCLUSIONS: Our results identified a new nucleic acid-based agent (CD8 aptamer-GNLY siRNA chimera) that can significantly inhibit CTL-mediated drug hypersensitivity, such as that seen in patients with SJS/TEN, as well as the alloreactivity seen in patients with GVHD. This study provides a novel therapeutic strategy for CTL-mediated immune disorders.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Allergy Clin Immunol

DOI

EISSN

1097-6825

Publication Date

September 2013

Volume

132

Issue

3

Start / End Page

713 / 722.e11

Location

United States

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • Stevens-Johnson Syndrome
  • RNA, Small Interfering
  • Humans
  • Graft vs Host Disease
  • CD8 Antigens
  • Aptamers, Nucleotide
  • Antigens, Differentiation, T-Lymphocyte
  • Allergy
  • 1107 Immunology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, C.-W., Chung, W.-H., Cheng, Y.-F., Ying, N.-W., Peck, K., Chen, Y.-T., & Hung, S.-I. (2013). A new nucleic acid-based agent inhibits cytotoxic T lymphocyte-mediated immune disorders. J Allergy Clin Immunol, 132(3), 713-722.e11. https://doi.org/10.1016/j.jaci.2013.04.036
Wang, Chuang-Wei, Wen-Hung Chung, Yi-Fang Cheng, Nien-Wen Ying, Konan Peck, Yuan-Tsong Chen, and Shuen-Iu Hung. “A new nucleic acid-based agent inhibits cytotoxic T lymphocyte-mediated immune disorders.J Allergy Clin Immunol 132, no. 3 (September 2013): 713-722.e11. https://doi.org/10.1016/j.jaci.2013.04.036.
Wang C-W, Chung W-H, Cheng Y-F, Ying N-W, Peck K, Chen Y-T, et al. A new nucleic acid-based agent inhibits cytotoxic T lymphocyte-mediated immune disorders. J Allergy Clin Immunol. 2013 Sep;132(3):713-722.e11.
Wang, Chuang-Wei, et al. “A new nucleic acid-based agent inhibits cytotoxic T lymphocyte-mediated immune disorders.J Allergy Clin Immunol, vol. 132, no. 3, Sept. 2013, pp. 713-722.e11. Pubmed, doi:10.1016/j.jaci.2013.04.036.
Wang C-W, Chung W-H, Cheng Y-F, Ying N-W, Peck K, Chen Y-T, Hung S-I. A new nucleic acid-based agent inhibits cytotoxic T lymphocyte-mediated immune disorders. J Allergy Clin Immunol. 2013 Sep;132(3):713-722.e11.
Journal cover image

Published In

J Allergy Clin Immunol

DOI

EISSN

1097-6825

Publication Date

September 2013

Volume

132

Issue

3

Start / End Page

713 / 722.e11

Location

United States

Related Subject Headings

  • T-Lymphocytes, Cytotoxic
  • Stevens-Johnson Syndrome
  • RNA, Small Interfering
  • Humans
  • Graft vs Host Disease
  • CD8 Antigens
  • Aptamers, Nucleotide
  • Antigens, Differentiation, T-Lymphocyte
  • Allergy
  • 1107 Immunology