期刊
IMMUNOBIOLOGY
卷 219, 期 1, 页码 17-24出版社
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.imbio.2013.06.008
关键词
CD4(+)CD25(+) regulatory T cells; lndolamine 2,3-dioxygenase; Antigen specific immune tolerance; Transplantation; Allogeneic immune response; Transplantation
类别
资金
- Transplant Research Foundation of British Columbia
- Canadian Institute of Health Research
- Spectra Energy
- CIHR Transplant Training Program
- WorkSafe BC Research Training Award
- Juvenile Diabetes Research Foundation
Regulatory CD4(+)CD25(+)Foxp3(+) T cells (Tregs) can be induced and expanded by dendritic cells (DCs) in the presence of the enzyme indoleamine 2,3-dioxygenase (IDO). Here we report that a possible alternative to DCs are IDO expressing dermal fibroblasts (DFs), which are easier to isolate and sustain in culture compared to DCs. When mouse splenocytes were co-cultured with IDO expressing DFs, a significant increase in frequency and the number of Tregs was found compared to those of control group (13.16% 1.8 vs. 5.53%+/- 1.2, p<0.05). Despite observing a higher total number of dead CD4(+) cells in the IDO group, there was a more abundant live CD4(+)CD25(+) subpopulation in this group. Further analysis reveales that these CD4(+) CD25(+) cells have the capacity to expand in the presence of IDO expressing DFs. Greater number of CTLA-4(+) cells and high expression of TGF-beta and IL-10 were found in CD4(+) cells of the IDO group compared to those of the controls. This finding confirmed a suppressive functionality of the expanded Tregs. Furthermore, CD4(+) CD25(+) cells isolated from the IDO group showed an alloantigen specific suppressive effect in a mixed lymphocyte reaction assay. These results confirm that IDO expressing dermal fibroblasts can expand a population of suppressive antigen specific Tregs. In conclusion, IDO expressing dermal fibroblasts have the capacity to stimulate the expansion of a subset of Tregs which can be used to generate antigen-specific immune tolerance. (C) 2013 Elsevier GmbH. All rights reserved.
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