In:
The Journal of Immunology, The American Association of Immunologists, Vol. 182, No. 1_Supplement ( 2009-04-01), p. 50.27-50.27
Abstract:
Manipulation of CD4+CD25+FOXP3+ Treg cells may be a valuable new approach to therapy for transplantation and autoimmunity. We report the first data involving epigenetic modulation of the suppressive functions of human Tregs. CD4+CD25- T cells and CD4+CD25+ Treg cells from 14 healthy donors were isolated by magnetic beads. CFSE-labeled CD4+CD25- T cells were stimulated with CD3 mAb and irradiated PBMC, co-cultured for 3-4 d with Tregs and varying concentrations of HDACi (sodium butyrate, valproic acid) and/or DNMTi (decitabine, zebularine, RG108), and cell divisions determined by CFSE dilution. Control wells without drugs provided serial suppression data specific for each donor, and wells without Tregs showed maximal cell divisions that were not markedly impaired by drugs. We found that HDACi or DNMTi directly increased expression of Foxp3 and Foxp3-dependent genes and increased the suppressive activity of human Tregs by up to 3-fold (p & lt;0.05). This approach also markedly improved outcomes in parallel studies of murine Tregs in vitro and in vivo, including in murine models of autoimmunity and transplant rejection. We conclude that epigenetic-based therapies using clinically approved drugs may provide the means to usefully upregulate Treg functions in patients with autoimmunity or post-transplantation.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.182.Supp.50.27
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2009
detail.hit.zdb_id:
1475085-5
