Chapter title |
Suppression and Regulation of Immune Responses
|
---|---|
Chapter number | 5 |
Book title |
Suppression and Regulation of Immune Responses
|
Published in |
Methods in molecular biology, January 2016
|
DOI | 10.1007/978-1-4939-3139-2_5 |
Pubmed ID | |
Book ISBNs |
978-1-4939-3138-5, 978-1-4939-3139-2
|
Authors |
Zavala, Flora, Korniotis, Sarantis, Montandon, Ruddy, Flora Zavala, Sarantis Korniotis, Ruddy Montandon |
Abstract |
Control of T-cell responses can be achieved by several subsets of B cells with immunoregulatory functions, mostly acting by provision of the anti-inflammatory cytokine IL-10 or exhibiting killing properties through Fas ligand (Fas-L) or granzyme B-induced cell death. We herein describe the characterization as well as the cellular and molecular mechanisms mediating the suppressive properties of bone marrow immature innate pro-B cell progenitors that emerge upon transient activation of Toll-like receptor 9. They are licensed by activated T-cell-derived IFN-γ to become suppressive by up-regulating their Fas-L expression and inducing effector CD4(+) T-cell apoptosis. They also up-regulate their own IFN-γ production which dramatically reduces T-cell production of a major pathogenic cytokine, IL-21. A single adoptive transfer of as little as 60,000 of them efficiently prevents the onset of spontaneous type 1 diabetes in recipient nonobese diabetes (NOD) mice, highlighting the remarkable regulatory potency of these so-called CpG-proB cell progenitors compared to regulatory cells of diverse lineages so far described. The CpG-proB cell activity is prolonged in vivo by their differentiation after migration in the pancreas and the spleen into B-cell progeny with high Fas-L expression that can keep up inducing apoptosis of effector T cells in the long term. |
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