Adoptively transferred Tregs accumulate in a site-specific manner and ameliorate signs of less advanced collagen-induced arthritis progress in rats

Immunotherapy. 2015;7(3):215-28. doi: 10.2217/imt.14.121.

Abstract

Aim: The aim of the study was to assess the therapeutic effect and migration of adoptively transferred Tregs in the course of collagen-induced arthritis (CIA) in rats.

Methods: Sorted CD4(+)CD25(+) cells were cultured in the presence of 17-β-estradiol, stained with CellTracker and then administered into the articular capsule of ankle joint of animals in different stages of CIA progression.

Results: Tregs diminished CIA signs only in animals with less advanced disease progress. Moreover, migration of transferred cells into the LN in the near proximity of the injection site and with distal location was almost completely stopped in animals with fully developed CIA.

Conclusion: Disease progression-related differences in migratory potential of in vitro induced Tregs may be responsible for the failure of cellular therapy during the advanced stages of CIA.

Keywords: adoptive transfer; collagen-induced arthritis; estrogen; foxp3; regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / therapy*
  • Cells, Cultured
  • Disease Progression
  • Estradiol / metabolism
  • Female
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Joints / immunology
  • Organ Specificity
  • Rats
  • Rats, Wistar
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / transplantation

Substances

  • Interleukin-2 Receptor alpha Subunit
  • Estradiol