Background/Purpose:

Interplay between Foxp3⁺ regulatory T cells (Treg) and dendritic cells (DCs) maintains immunologic tolerance, but the effects of each cell on the other are not well understood.

Methods:

Naive CD4+Foxp3- cells isolated from DBA/2 mice were stimulated with anti-CD3/CD28 antibodies with IL-2 and TGF-β to develop polyclonal CD4+ iTregs. These cells were adoptively transferred to D2B6F1 mice that also received D2 spleen cells. Anti-IL-10R, Anti-TGFβ or ALK5 (TGFβRI) inhibitor was administrated in some groups of mice. To determine molecular mechanism, TGFβRII DC conditional KO mice were developed and colitis model was used. DC numbers and phenotypes were determined in chronic lupus mice before and after iTreg or Tcon cell treatment. DC were sorted in iTreg or Tcon treated groups and were adoptively transferred to another lupus mice to determine the therpeutic role of DC subsets. 

Results:

We report that polyclonal CD4⁺Foxp3⁺ Treg cells induced ex-vivo with TGFβ (iTreg) suppress a lupus-like chronic graft-versus-host disease by preventing the expansion of immunogenic DCs and inducing protective DCs that generate additional recipient CD4⁺Foxp3⁺ cells. The protective effects of the transferred iTreg cells required both IL-10 and TGFβ, but the tolerogenic effects of the iTreg on DCs, and the immunosuppressive effects of these DCs, was exclusively TGFβ-dependent.  The iTreg were unable to tolerize Tgfbr2-deficient DCs. 

Conclusion:

These results support the essential role of DCs in “infectious tolerance” and emphasize the central role of TGFβ in protective iTreg/DCs interactions in vivo.

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« Back to 2012 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/polyclonal-cd4foxp3-treg-cells-induce-tgfb-dependent-tolerogenic-dendritic-cells-that-suppress-murine-lupus-like-syndrome/