In:
The Journal of Immunology, The American Association of Immunologists, Vol. 182, No. 1_Supplement ( 2009-04-01), p. 89.34-89.34
Abstract:
CD8+ cells stimulated with IL-2 and TGF-β can be induced to develop suppressive activity. However, the phenotype and functional characteristics of these polyclonal regulatory T cells (iTregs) have not been well characterized. To distinguish expanded thymus-derived Foxp3+ CD8+ cells from conventional CD8+CD25- cells induced to become Foxp3+ Tregs, we used Foxp3 GFP transgenic mice. Splenic GFP- cells from these mice were stimulated with anti-CD3/28 coated beads. Following 4-day stimulation, 35% of CD8+ cells become CD25+GFP+ cells in the presence of IL-2 and TGF-β. Granzyme B expression was decreased compared to CD8+ cells activated without TGF-β. These cells were also anergic following restimulation. Although their Foxp3 expression is lower than TGF-β -induced CD4+ cells, they displayed similar suppressive activity in cell contact-dependent, non-cytotoxic suppressive activity manner in a standard in vitro assay. Neutralization of TGF-β, IL-10 or IL-10 receptor and the TGF-β receptor I (ALK5) inhibitor was unable to abolish the suppressive activity. Similar to CD4+ iTregs, adoptive transfer of CD8+ iTregs suppressed a chronic GVHD with a lupus-like syndrome. Thus, TCR stimulation with IL-2 and TGF-β can induce CD8+ cells as well as CD4+ cells to become Foxp3+ Treg cells and both of these subsets have protective effects against pathologic immune-mediated inflammation. (Supported by ACR REF Award and Outstanding youth Scientist Award from NSFC)
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.182.Supp.89.34
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2009
detail.hit.zdb_id:
1475085-5
