Engineered antigen-specific human regulatory T cells: Immunosuppression of FVIII-specific T- and B-cell responses

Yong Chan Kim, Ai Hong Zhang, Yan Su, Sadiye Amcaoglu Rieder, Robert J. Rossi, Ruth A. Ettinger, Kathleen P. Pratt, Ethan M. Shevach, David W. Scott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

129 Scopus citations

Abstract

Expansion of human regulatory T cells (Tregs) for clinical applications offers great promise for the treatment of undesirable immune responses in autoimmunity, transplantation, allergy, and antidrug antibody responses, including inhibitor responses in hemophilia A patients. However, polyclonal Tregs are nonspecific and therefore could potentially cause global immunosuppression. To avoid this undesirable outcome, the generation of antigen-specific Tregswould be advantageous. Herein,we report the production and properties of engineered antigen-specific Tregs, created by transduction of a recombinant T-cell receptor obtained from a hemophilia A subject's T-cell clone, into expanded human FoxP3+ Tregs. Such engineered factor VIII (FVIII)-specific Tregs efficiently suppressed the proliferation and cytokine production of FVIII-specific T-effector cells. Moreover, studies with an HLA-transgenic, FVIII-deficient mouse model demonstrated that antibody production from FVIII-primed spleen cells in vitro were profoundly inhibited in the presence of these FVIII-specific Tregs, suggesting potential utility to treat anti-FVIII inhibitory antibody formation in hemophilia A patients. (Blood.

Original languageEnglish
Pages (from-to)1107-1115
Number of pages9
JournalBlood
Volume125
Issue number7
DOIs
StatePublished - 12 Feb 2015
Externally publishedYes

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