Journal
IMMUNOLOGY AND CELL BIOLOGY
Volume 96, Issue 8, Pages 852-862Publisher
WILEY
DOI: 10.1111/imcb.12053
Keywords
Apoptosis; B cells; Helios; Neuropilin-1; PD-1; Treg
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Funding
- Central Animal Facilities
- Flow Cytometry Core Facility of the medical Faculty of Bonn University
- Deutsche Forschungsgemeinschaft (DFG Grant) [Lu1387/2-1, SFBTR57, SFB1192]
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Regulatory T cells (Tregs) maintain self-tolerance and prevent autoimmunity by controlling autoreactive T cells. We recently demonstrated invivo that Tregs can directly suppress auto-reactive B cells via programmed death ligand 1 (PD-L1) that ligated PD-1 on B cells and caused them to undergo apoptosis. Here, we asked whether this mechanism is utilized by thymus-derived natural Tregs and/or by peripheral lymphoid tissue-induced Tregs. We first demonstrated that antigen-specific PD-L1-expressing Tregs were induced in the draining lymph node of autoantigen-expressing tissue and characterized them by their lack of the transcription factor Helios and of the surface marker Neuropilin-1 (Nrp-1). Next, we established an invitro co-culture system to study the interaction between B cells and Treg subsets under controlled conditions. We found that Nrp(-) Treg, but not Nrp(+) Treg suppressed autoreactive B cells, whereas both were able to suppress T-helper cells. Such suppression was antigen-specific and was facilitated by PD-L1/PD-1-induced apoptosis. Furthermore, it required physical cell contact and was MHC II-restricted, providing an explanation for the antigen-specificity of peripherally-induced Tregs. These findings identify a role for peripherally induced Helios(-) Nrp-1(-) inducible Treg in controlling peripheral B-cell tolerance against tissue auto-antigens.
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