Title: In Vivo Induction of Type 1-Like Regulatory T Cells Using Genetically Modified B Cells Confers Long-Term IL-10-Dependent Antigen-Specific Unresponsiveness
Authors: Ahangarani, Roxana Roohi ×
Janssens, Wim
Vander Elst, Luc
Carlier, Vincent
Vandendriessche, Thierry
Chuah, Marinee
Weynand, Birgit
Vanoirbeek, Jeroen
Jacquemin, Marc
Saint-Remy, Jean-Marie #
Issue Date: Dec-2009
Publisher: American Association of Immunologists
Series Title: Journal of Immunology vol:183 issue:12 pages:8232-43
Abstract: Regulatory T cells (Tregs) hold much promise for the therapy of allergy and autoimmunity, but their use is hampered by lack of Ag specificity (natural Tregs) and difficulty to expand in vitro or in vivo (adaptive Tregs). We designed a method for in vivo induction of Ag-specific Tregs, in BALB/c H-2d, that share characteristics with type 1 Tregs (Tr1). A retroviral vector was constructed encoding a major T cell epitope of a common allergen, Der p 2, fused to an endosomal targeting sequence (gp75) for efficient MHC class II presentation. B cells transduced with such construct were adoptively transferred to BALB/c mice before or after peptide immunization. Long-lasting Ag-specific immune tolerance was achieved in both cases. Genetically modified B cells constitutively expressed the transgene for at least 3 mo. B cells from IL-10(-/-) mice were unable to induce tolerance. Upon transfer, B cells induced Foxp3(-)CD4(+) T cells showing phenotypic and functional characteristics comparable to Tr1-cells, including production of IL-10 but not of TGF-beta, and high expression of CTLA-4. Adoptive transfer of such T cells conferred unresponsiveness to allergen immunization and prevented the development of Der p 2-induced asthma. Functional Tr1-like cells can therefore be induced in vivo using retrovirally transduced B cells.
ISSN: 0022-1767
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Occupational, Environmental and Insurance Medicine (-)
Molecular and Vascular Biology
× corresponding author
# (joint) last author

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