In vitro Expansion of Natural Regulatory T Lymphocytes Useful for Cell Therapy in Allotransplantation.
10.4167/jbv.2009.39.3.217
- Author:
Youn Hee PARK
1
;
Sun Kyung KOO
;
Yu Joung LEE
;
In Yi JOE
;
Song Cheol KIM
;
Duck Jong HAN
;
Dong Gyun LIM
Author Information
1. Department of Surgery, Ulsan University College of Medicine & Asan Medical Center, Asan Institute for Life Sciences, Seoul, Korea. dglim@amc.seoul.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Regulatory T lymphocyte;
Cell therapy;
Allograft rejection;
Ex vivo expansion
- MeSH:
Animals;
Cytokines;
Dendritic Cells;
Humans;
Immunotherapy;
Interleukin-2;
Mice;
Receptors, Lymphocyte Homing;
Rejection (Psychology);
Skin;
T-Lymphocytes;
T-Lymphocytes, Regulatory;
Tissue Donors;
Tissue Therapy;
Transplantation, Homologous
- From:Journal of Bacteriology and Virology
2009;39(3):217-227
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Immunotherapy with regulatory T lymphocytes is considered to be an attractive new therapeutic modality to prevent allograft rejection. The success of this new therapy is critically dependent on the preparation of highly effective and enough number of regulatory T cells. Here, we tried to establish a proper strategy for the ex vivo expansion of regulatory T cells and evaluated their characteristics. CD4+CD25h+CD62L+ T cells were isolated from the recipient mice and weekly stimulated with various stimuli in the presence of IL-2. The most efficient protocol for the expansion of regulatory T cells maintaining Foxp3 expression and regulatory activity was the three cycles stimulation with donor bone marrow-derived dendritic cells (BM-DCs) which yielded around 400 fold expansion of regulatory T cells. The in vitro-expanded regulatory T cells expressing lymph node homing receptors on their cell surface, were composed of polyclonal population, and did not acquire the ability to produce effector cytokines. Importantly, these expanded regulatory T cells induced a modest prolongation of skin allograft survival when combined with transient T cell depletion in recipient mice. These data indicate that our protocol could be used to obtain an effective population of natural regulatory T cells available for the regulatory T cell therapy to prevent allograft rejection.