What question did this study set out to answer?

To determine whether forced co-expression of FoxP3 prevents TCR-engineered regulatory T cells from losing their suppressive phenotype and converting into pathogenic effector T cells.

August 29, 2022Journal of AutoimmunityOpen Access

Forced Fox-P3 expression can improve the safety and antigen-specific function of engineered regulatory T cells

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Authors

JMJenny L. McGoverne-Therapeutics (United Kingdom)AHAngelika HollerInstitute of Infection and Immunity STSharyn ThomasInstitute of Infection and Immunity

Discussion

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Implication

Preclinical study reveals that co-expressing FoxP3 stabilizes antigen-specific regulatory T cells in transgenic mice, indicating a safer approach for treating autoimmune disease.

Key Points

To determine whether forced co-expression of FoxP3 prevents TCR-engineered regulatory T cells from losing their suppressive phenotype and converting into pathogenic effector T cells.
Engineered a retroviral vector driving coordinated expression of FoxP3 and a human HLA-DR-restricted TCR in purified human regulatory T cells.
Assessed in vitro suppressive potency, proliferation, and phenotypic marker expression (CD25 and CTLA4).
Adoptively transferred engineered human Tregs into HLA-DR transgenic mice to examine engraftment, persistence, and phenotypic stability in vivo compared to TCR-only controls.
Transduced human Tregs exhibited elevated FoxP3, CD25, and CTLA4 expression, maintained potent suppressive function, and showed unimpaired in vitro expansion.
FoxP3+TCR engineered Tregs achieved long-term persistence in HLA-DR transgenic mice while reliably maintaining FoxP3 and TCR expression without effector conversion.
Tregs transduced with TCR alone lost FoxP3 expression in vivo and converted into antigen-responsive effector T cells upon peptide stimulation.

Cite This Study

McGovern et al. (2022) studied this question.

synapsesocial.com/papers/6aa0ee8f500b9604269d2d06 https://doi.org/10.1016/j.jaut.2022.102888

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Implication

Preclinical study reveals that co-expressing FoxP3 stabilizes antigen-specific regulatory T cells in transgenic mice, indicating a safer approach for treating autoimmune disease.

Forced Fox-P3 expression can improve the safety and antigen-specific function of engineered regulatory T cells

Discussion

Member takes

Implication

Key Points

Cite This Study

Forced Fox-P3 expression can improve the safety and antigen-specific function of engineered regulatory T cells

Discussion

Member takes

Implication

Key Points

Cite This Study

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