Porcine Treg depletion with a novel diphtheria toxin-based anti-human CCR4 immunotoxin

Zhaohui Wang, Nalu Navarro-Alvarez, Jigesh A. Shah, Huiping Zhang, Qi Huang, Qian Zheng, Joren C. Madsen, David H. Sachs, Christene A. Huang, Zhirui Wang

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Regulatory T cells (Tregs) are known to play an important role in immunoregulation and have been shown to facilitate induction of transplantation tolerance. Chemokine (C-C motif) receptor 4 (CCR4) is expressed on the surface of effector Tregs involved in controlling alloimmune and autoimmune responses. Recently we have developed a novel diphtheria-toxin based anti-human CCR4 immunotoxin for depleting CCR4+ cells in vivo. In this study, we have demonstrated that the anti-human CCR4 immunotoxin bound to porcine lymphocytes including CD4+FoxP3+ Tregs. Anti-human CCR4 immunotoxin effectively depleted CCR4+ Foxp3+ porcine Tregs in vivo. We observed depletion of up to 70–85% of the CCR4+Foxp3+ porcine Tregs in the peripheral blood and 85–91% in the lymph nodes following the anti-human CCR4 immunotoxin treatment in Massachusetts General Hospital (MGH) miniature swine. The depletion lasted for about one week with no significant reduction observed within CCR4 cell populations including CD8α+ T cells, CCR4CD4+ T cells and B cells. In summary, anti-human CCR4 immunotoxin effectively depleted CCR4+Foxp3+ porcine Tregs in both peripheral blood and lymph nodes.

Original languageEnglish (US)
Pages (from-to)150-158
Number of pages9
JournalVeterinary Immunology and Immunopathology
Volume182
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

Keywords

  • CCR4
  • Diphtheria toxin
  • Immunotoxin
  • MGH miniature swine
  • Porcine Treg

ASJC Scopus subject areas

  • Immunology
  • veterinary(all)

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