AI Article Synopsis
- The study demonstrates that using antigen-specific regulatory T cells (Treg) is more effective at suppressing immune responses in transplant scenarios than polyclonal Treg.
- Researchers created large numbers of Treg by genetically modifying CD4+CD25- cells to express the foxp3 gene, which allowed these induced Treg to function similarly to naturally occurring Treg.
- The findings suggest that by controlling the specificity and potency of these Treg, it could improve strategies for achieving immune tolerance in transplant patients.
Article Abstract
Adoptive transfer of polyclonal CD4+CD25+ regulatory T cells (Treg) can tolerize transplantation alloresponses. Treg are activated via their specific TCR, but the antigen specificity of wild-type Treg remains elusive, and therefore controlling potency and duration of Treg activity in the transplantation setting is still not feasible. In this study, we used murine graft-versus-host disease (GVHD) as a model system to show that antigen-specific Treg suppress the response of T effector cells to alloantigens in vitro and prevent GVHD in vivo. The suppressive potential of antigen-specific Treg was much greater than that of polyclonal Treg. To acquire large numbers of antigen-specific Treg, we transduced CD4+CD25- cells with foxp3, and found that these foxp3-induced Treg suppress alloresponses in vitro and prevent GVHD in vivo as effectively as naturally derived CD4+CD25+ Treg. Furthermore, we used an antigen-specific CD4 Th1 clone as a source of foxp3-induced Treg after transduction with foxp3, and found those Treg to effectively prevent GVHD in an antigen-dependent manner. The findings of this study provide a basis for the concept that the onset and potency of the suppression by Treg can be regulated, and suggest a novel approach to enhance the feasibility and effectiveness of inducing tolerance by Treg as an adoptive immunotherapy in transplantation.
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| http://dx.doi.org/10.1002/eji.200526077 | DOI Listing |
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