Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 47, Issue 12, Pages 2153-2162Publisher
WILEY
DOI: 10.1002/eji.201747137
Keywords
Adoptive T cell transfer; Graft-versus-host-disease; Regulatory T cells; Reversible multimer staining; T-cell therapy
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Funding
- TUM Institute for Advanced Study
- [SFB TR36 (TP-A10/13)]
- [SFB 1054 (TP-B09)]
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The transfer of regulatory T cells, either freshly isolated, or modified, represents a promising therapeutic approach to dampen misdirected immune responses, like autoimmune diseases, chronic inflammatory syndromes and graft versus host disease. Clinical isolation of highly pure regulatory T cell (Treg) populations is still challenging and labeling reagents can influence their viability and functionality, potentially altering the potency of isolated Treg cell products. Here we show that reversible Fab multimer-based Treg purification can prevent conventional antibody label-induced interferences in vitro and in vivo. Remaining isolation reagents negatively interfere with Treg engraftment efficacy in C57BL/6 wild-type mice due to Fc gamma-receptor- as well as IL-2 receptor-mediated mechanisms. Using a preclinical model for acute GvHD, we further show that purified 'label-freed' Tregs are protective at substantially lower cell numbers as compared to conventional nonreversible antibody staining, translating into significantly improved survival of mice treated with minimally manipulated Tregs. These findings have important clinical relevance for future Treg-based cell therapies.
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