In vitro polyclonal activation of conventional T cells with a CD28 superagonist protects mice from acute graft versus host disease |
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| Authors: | Niklas Beyersdorf Sandra Werner Nelli Wolf Thomas Hünig Thomas Kerkau |
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| Affiliation: | Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany |
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| Abstract: | Upon transplantation of T cells from a CD28 superagonist (CD28‐SA) treated donor into an irradiated allogeneic host, the CD28‐SA‐induced activation and expansion of Treg cells inhibits acute graft versus host disease (aGvHD), while not abrogating the desired graft versus tumor effect. Human peripheral blood CD4+ T cells, however, harbor only very few Treg cells. Therefore, we studied whether polyclonal in vitro prestimulation of conventional, that is Treg‐cell‐depleted, CD4+ T cells of C57BL/6 mice with CD28‐SA‐coated paramagnetic beads is sufficient to protect recipient BALB/c mice from aGvHD. CD28‐SA prestimulation of conventional CD4+ T cells efficiently protected BALB/c recipient mice from aGvHD and CD28‐SA‐stimulated CD4+ and CD8+ T cells were capable of mediating long‐term protection from the BCL1 lymphoma. The recently completed successful phase I testing of the human CD28‐SA TGN1412/TAB08 should greatly facilitate further development of this straightforward method into a novel immunotherapy for patients. |
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| Keywords: | aGvHD Conventional T cells CD28 superagonist GvT effect |
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