GM-CSF-induced, bone-marrow-derived dendritic cells can expand natural Tregs and induce adaptive Tregs by different mechanisms

Journal of Leukocyte Biology

Jian Rong Sheng  and¹  Anupama Gopisetty¹  Bellur S. Prabhakar¹  Balaji B. Ganesh¹  Palash Bhattacharya¹ 

[1] Departments of Microbiology and Immunology and  Neurology, University of Illinois at Chicago, Chicago, Illinois, USA

关键词: T cells;    autoimmunity;    Foxp3;    OX40-OX40L;    TGF-β;   

DOI  :  10.1189/jlb.0310154

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

In our earlier work, we had shown that GM-CSF treatment of CBA/J mice can suppress ongoing thyroiditis by inducing tolerogenic CD8α− DCs, which helped expand and/or induce CD4+Foxp3+ Tregs. To identify the primary cell type that was affected by the GM-CSF treatment and understand the mechanism by which Tregs were induced, we compared the effect of GM-CSF on matured spDCs and BMDC precursors in vitro. Matured spDCs exposed to GM-CSF ex vivo induced only a modest increase in the percentage of Foxp3-expressing T cells in cocultures. In contrast, BM cells, when cultured in the presence of GM-CSF, gave rise to a population of CD11c+CD11bHiCD8α− DCs (BMDCs), which were able to expand Foxp3+ Tregs upon coculture with CD4+ T cells. This contact-dependent expansion occurred in the absence of TCR stimulation and was abrogated by OX40L blockage. Additionally, the BMDCs secreted high levels of TGF-β, which was required and sufficient for adaptive differentiation of T cells to Foxp3+ Tregs, only upon TCR stimulation. These results strongly suggest that the BMDCs differentiated by GM-CSF can expand nTregs and induce adaptive Tregs through different mechanisms.

【 授权许可】

Unknown