GM-CSF-induced, bone-marrow-derived dendritic cells can expand natural Tregs and induce adaptive Tregs by different mechanisms.
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(+)CD11b(Hi)CD8α(-) 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.
Department of Microbiology and Immunology, University of Illinois, Chicago, Chicago, IL 60612, USA.
Palash
P
Bhattacharya
Anupama
A
Gopisetty
Balaji B
BB
Ganesh
Jian Rong
JR
Sheng
Bellur S
BS
Prabhakar
D056704:Adaptive Immunity; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D007108:Immune Tolerance; D018655:Lymphocyte Count; D054503:Lymphoid Progenitor Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D016178:Granulocyte-Macrophage Colony-Stimulating Factor