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Updated: Jul 16, 2026
07:17
Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
Published on: June 22, 2016
Effector and regulatory T-cell function is differentially regulated by RelB within antigen-presenting cells during
Kelli P A MacDonald1, Rachel D Kuns, Vanessa Rowe
1Bone Marrow Transplantation Laboratory, Queensland Institute of Medical Research, 300 Herston Road, Herston, QLD 4006, Australia.
Blood
|March 1, 2007
Summary
Graft-versus-host disease (GVHD) severity is reduced by inhibiting RelB in antigen-presenting cells (APCs). This targeted inhibition dissociates effector and regulatory T-cell responses, offering a potential therapeutic strategy for Th1-mediated tissue injury.
Area of Science:
- Immunology
- Cell Biology
- Transplantation Medicine
Background:
- Antigen-presenting cells (APCs) initiate graft-versus-host disease (GVHD), but the specific APC subset and molecular drivers are not fully understood.
- Dendritic cells (DCs) are potent APCs, and the transcription factor RelB is linked to DC maturation and function.
Purpose of the Study:
- To investigate the role of RelB in dendritic cells (DCs) and its involvement in the initiation and progression of GVHD.
- To explore the potential of targeting RelB in APCs as a therapeutic strategy for GVHD.
Main Methods:
- Examined RelB nuclear translocation in host APCs post-irradiation.
- Assessed the impact of transient depletion of CD11c(hi) donor DCs on GVHD severity.
- Utilized RelB knockout (RelB-/-) bone marrow chimeras as recipients and donors to evaluate GVHD dependence on RelB in APCs.
- Analyzed the effect of RelB on donor T cell expansion and function (Th1 and FoxP3+ regulatory T cells).
Main Results:
- RelB nuclear translocation increased in host CD11c(hi) DCs within 4 hours of irradiation.
- Transient depletion of CD11c(hi) donor DCs led to a temporary decrease in GVHD severity.
- GVHD induction and maintenance were critically dependent on RelB in both host and donor APCs.
- RelB in APCs was essential for the expansion of donor Th1 effector cells and alloreactivity, but not for regulatory T cell expansion or function.
Conclusions:
- RelB within APCs plays a critical role in driving GVHD by promoting Th1 effector cell expansion.
- Targeted inhibition of nuclear RelB translocation in APCs could be a promising therapeutic approach to manage GVHD.
- This strategy may allow for the dissociation of effector and regulatory T cell responses, mitigating Th1-mediated tissue injury.
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