Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 89, Issue 2, Pages 235-249Publisher
WILEY
DOI: 10.1189/jlb.0310154
Keywords
T cells; autoimmunity; Foxp3; OX40-OX40L; TGF-beta
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Funding
- National Institutes of Health [AI 058190]
- University of Illinols at Chicago (UIC) Center for Clinical and Translational Science (CCTS) from the National Center for Research Resources [UL1RR029879]
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In our earlier work, we had shown that GM-CSF treatment of CBA/J mice can suppress ongoing thyroiditis by inducing tolerogenic CD8 alpha(-) 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(+)CD11b(Hi)CD8 alpha(-) 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-beta, 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. J. Leukoc. Biol. 89: 235-249; 2011.
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