scholarly journals Crucial roles of B7-H1 and B7-DC expressed on mesenteric lymph node dendritic cells in the generation of antigen-specific CD4+Foxp3+ regulatory T cells in the establishment of oral tolerance

Blood ◽  
2010 ◽  
Vol 116 (13) ◽  
pp. 2266-2276 ◽  
Author(s):  
Tomohiro Fukaya ◽  
Hideaki Takagi ◽  
Yumiko Sato ◽  
Kaori Sato ◽  
Kawori Eizumi ◽  
...  

Abstract Oral tolerance is a key feature of intestinal immunity, generating systemic tolerance to fed antigens. However, the molecular mechanism mediating oral tolerance remains unclear. In this study, we examined the role of the B7 family members of costimulatory molecules in the establishment of oral tolerance. Deficiencies of B7-H1 and B7-DC abrogated the oral tolerance, accompanied by enhanced antigen-specific CD4+ T-cell response and IgG1 production. Mesenteric lymph node (MLN) dendritic cells (DCs) displayed higher levels of B7-H1 and B7-DC than systemic DCs, whereas they showed similar levels of CD80, CD86, and B7-H2. MLN DCs enhanced the antigen-specific generation of CD4+Foxp3+ inducible regulatory T cells (iTregs) from CD4+Foxp3− T cells rather than CD4+ effector T cells (Teff) relative to systemic DCs, owing to the dominant expression of B7-H1 and B7-DC. Furthermore, the antigen-specific conversion of CD4+Foxp3− T cells into CD4+Foxp3+ iTregs occurred in MLNs greater than in peripheral organs during oral tolerance under steady-state conditions, and such conversion required B7-H1 and B7-DC more than other B7 family members, whereas it was severely impaired under inflammatory conditions. In conclusion, our findings suggest that B7-H1 and B7-DC expressed on MLN DCs are essential for establishing oral tolerance through the de novo generation of antigen-specific CD4+Foxp3+ iTregs.

Immunology ◽  
2017 ◽  
Vol 152 (1) ◽  
pp. 52-64 ◽  
Author(s):  
Aya Shiokawa ◽  
Ryutaro Kotaki ◽  
Tomohiro Takano ◽  
Haruyo Nakajima-Adachi ◽  
Satoshi Hachimura

2017 ◽  
Vol 47 (12) ◽  
pp. 2142-2152 ◽  
Author(s):  
Maria Pasztoi ◽  
Joern Pezoldt ◽  
Michael Beckstette ◽  
Christoph Lipps ◽  
Dagmar Wirth ◽  
...  

2008 ◽  
Vol 180 (10) ◽  
pp. 6501-6507 ◽  
Author(s):  
Raul Elgueta ◽  
Fernando E. Sepulveda ◽  
Felipe Vilches ◽  
Leonardo Vargas ◽  
J. Rodrigo Mora ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Jiale Qu ◽  
Xiuxue Yu ◽  
Chenxi Jin ◽  
Yuanfa Feng ◽  
Shihao Xie ◽  
...  

Toll-like receptors (TLRs) play an important role in regulating immune responses during pathogen infection. However, roles of TLRs on T cells reside in the mesenteric lymph node (MLN) were not be fully elucidated in the course of S. japonicum infection. In this study, T lymphocytes from the mesenteric lymph node (MLN) of S. japonicum-infected mice were isolated and the expression and roles of TLR2, TLR3, TLR4, and TLR7 on both CD4+ and CD8+ T cells were compared. We found that the expression of TLR7 was increased in the MLN cells of S. japonicum-infected mice, particularly in CD4+ and CD8+ T cells (P<0.05). R848, a TLR7 agonist, could enhance the production of IFN-γ from MLN T cells of infected mice (P<0.05), especially in CD8+ T cells (P<0.01). In TLR7 gene knockedout (KO) mice, the S. japonicum infection caused a significant decrease (P<0.05) of the expression of CD25 and CD69, as well as the production of IFN-γ and IL-4 inducted by PMA plus ionomycin on both CD4+ and CD8+ T cells. Furthermore, the decreased level of IFN-γ and IL-4 in the supernatants of SEA- or SWA-stimulated mesenteric lymphocytes was detected (P<0.05). Our results indicated that S. japonicum infection could induce the TLR7 expression on T cells in the MLN of C57BL/6 mice, and TLR7 mediates T cell response in the early phase of infection.


2011 ◽  
Vol 186 (12) ◽  
pp. 6999-7005 ◽  
Author(s):  
Jae-Hoon Chang ◽  
Hye-Ran Cha ◽  
Sun-Young Chang ◽  
Hyun-Jeong Ko ◽  
Sang-Uk Seo ◽  
...  

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