Long-Term Engraftment of Human Natural T Regulatory Cells in NOD/SCID IL2rγcnull Mice by Expression of Human IL-2

Sojan Abraham, Rajendra Pahwa, Chunting Ye, Jang gi Choi, Savita Pahwa, Shashidhar Jaggaiahgari, Ashwin Raut, Shuiping Chen, N. Manjunath, Premlata Shankar

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Regulatory T cells are essential to maintain immune homeostasis and prevent autoimmunity. Therapy with in vitro expanded human nTRegs is being tested to prevent graft versus host disease, which is a major cause for morbidity and mortality associated with hematopoietic stem cell transplantation. Their usefulness in therapy will depend on their capacity to survive, migrate appropriately and retain suppressive activity when introduced into a transplant recipient. The lack of a suitable animal model for studying the in vivo reconstitutive capability of human nTRegs is a major impediment for investigating the behavior of adoptively transferred nTRegs in vivo. We show that injection of a plasmid encoding human IL-2 is necessary and sufficient for long term engraftment of in vitro expanded nTRegs in NOD-SCID IL2rγcnull mice. We also demonstrate that these in vivo reconstituted TRegs traffic to different organs of the body and retain suppressive function. Finally, in an IL-2 accelerated GVHD model, we show that these in vivo reconstituted TRegs are capable of preventing severe xenogenic response of human PBMCs. Thus, this novel 'hu-TReg mouse' model offers a pre-clinical platform to study the in vivo function and stability of human nTRegs and their ability to modulate autoimmune diseases and GVHD.

Original languageEnglish (US)
Article numbere51832
JournalPloS one
Volume7
Issue number12
DOIs
StatePublished - Dec 18 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Abraham, S., Pahwa, R., Ye, C., Choi, J. G., Pahwa, S., Jaggaiahgari, S., Raut, A., Chen, S., Manjunath, N., & Shankar, P. (2012). Long-Term Engraftment of Human Natural T Regulatory Cells in NOD/SCID IL2rγcnull Mice by Expression of Human IL-2. PloS one, 7(12), [e51832]. https://doi.org/10.1371/journal.pone.0051832