TGF-β-induced regulatory t cells directly suppress b cell responses through a noncytotoxic mechanism

Anping Xu, Ya Liu, Weiqian Chen, Julie Wang, Youqiu Xue, Feng Huang, Liming Rong, Jin Lin, Dahai Liu, Mei Yan, Quan Zhen Li, Bin Li, Jianxun Song, Nancy Olsen, Song Guo Zheng

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Foxp3+ regulatory T cells (Treg) playing a crucial role in the maintenance of immune tolerance and prevention of autoimmune diseases consist of thymus-derived naturally occurring CD4+Foxp3+ Treg cells (nTreg) and those that can be induced ex vivo with TGF-β (iTreg). Although both Treg subsets share similar phenotypes and functional characteristics, they also have potential biologic differences on their biology. The role of iTreg in regulating B cells remains unclear so far. The suppression assays of Treg subsets on activation, proliferation, and Abs production of B cells were measured using a Treg and B cell coculture system in vitro. Transwell and Ab blockade experiments were performed to assess the roles of cell contact and soluble cytokines. Treg were adoptively transferred to lupus mice to assess in vivo effects on B cells. Like nTreg, iTreg subset also directly suppressed activation and proliferation of B cells. nTreg subset suppressed B cell responses through cytotoxic manner related to expression of granzyme A, granzyme B, and perforin, whereas the role of iTreg subset on B cells did not involve in cytotoxic action but depending on TGFb signaling. Furthermore, iTreg subset can significantly suppress Ab produced by lupus B cells in vitro. Comparison experiments using autoantibodies microarrays demonstrated that adoptive transfer of iTreg had a superior effect than nTreg subset on suppressing lupus B cell responses in vivo. Our data implicate a role and advantage of iTreg subset in treating B cell-mediated autoimmune diseases, boosting the translational potential of these findings.

Original languageEnglish (US)
Pages (from-to)3631-3641
Number of pages11
JournalJournal of Immunology
Volume196
Issue number9
DOIs
StatePublished - May 1 2016

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B-Lymphocytes
Regulatory T-Lymphocytes
B-Lymphocyte Subsets
Autoimmune Diseases
Granzymes
Immune Tolerance
Adoptive Transfer
Coculture Techniques
Autoantibodies
Thymus Gland
Maintenance
Cytokines
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

TGF-β-induced regulatory t cells directly suppress b cell responses through a noncytotoxic mechanism. / Xu, Anping; Liu, Ya; Chen, Weiqian; Wang, Julie; Xue, Youqiu; Huang, Feng; Rong, Liming; Lin, Jin; Liu, Dahai; Yan, Mei; Li, Quan Zhen; Li, Bin; Song, Jianxun; Olsen, Nancy; Zheng, Song Guo.

In: Journal of Immunology, Vol. 196, No. 9, 01.05.2016, p. 3631-3641.

Research output: Contribution to journalArticle

Xu, A, Liu, Y, Chen, W, Wang, J, Xue, Y, Huang, F, Rong, L, Lin, J, Liu, D, Yan, M, Li, QZ, Li, B, Song, J, Olsen, N & Zheng, SG 2016, 'TGF-β-induced regulatory t cells directly suppress b cell responses through a noncytotoxic mechanism', Journal of Immunology, vol. 196, no. 9, pp. 3631-3641. https://doi.org/10.4049/jimmunol.1501740
Xu, Anping ; Liu, Ya ; Chen, Weiqian ; Wang, Julie ; Xue, Youqiu ; Huang, Feng ; Rong, Liming ; Lin, Jin ; Liu, Dahai ; Yan, Mei ; Li, Quan Zhen ; Li, Bin ; Song, Jianxun ; Olsen, Nancy ; Zheng, Song Guo. / TGF-β-induced regulatory t cells directly suppress b cell responses through a noncytotoxic mechanism. In: Journal of Immunology. 2016 ; Vol. 196, No. 9. pp. 3631-3641.
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