Journal
SEMINARS IN IMMUNOLOGY
Volume 23, Issue 6, Pages 462-468Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.smim.2011.07.008
Keywords
Regulatory T cell; Stem cell transplant; GVHD; Cellular therapy
Categories
Funding
- NIH [R01 CA72669, HL56067, AI34495, P01 CA142106, AI056299, CA067493]
- Leukemia and Lymphoma Translational Research Grant [R6029-07]
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Three main types of CD4+ regulatory T cells can be distinguished based upon whether they express Foxp3 and differentiate naturally in the thymus (natural Tregs) or are induced in the periphery (inducible Tregs); or whether they are FoxP3 negative but secrete IL-10 in response to antigen (Tregulatory type 1, Tr1 cells). Adoptive transfer of each cell type has proven highly effective in mouse models at preventing graft vs. host disease (GVHD) and autoimmunity. Although clinical application was initially hampered by low Treg frequency and unfavorable ex vivo expansion properties, several phase I trials are now being conducted to assess their effect on GVHD following hematopoietic stem cell transplantation (HSCT) and in type I diabetes. Human Treg trials for HSCT recipients have preceded other indications because GVHD onset is precisely known, the time period needed for prevention relatively short, initial efficacy is likely to provide life-long protection, and complications of GVHD can be lethal. This review will summarize the clinical trials conducted to date that have employed Tregs to prevent GVHD following HSCT and discuss recent advances in Treg cellular therapy. (C) 2011 Elsevier Ltd. All rights reserved.
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