Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 45, Issue 7, Pages 1997-2007Publisher
WILEY
DOI: 10.1002/eji.201445317
Keywords
aGvHD; Conventional T cells; CD28 superagonist; GvT effect
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Funding
- Wilhelm Sander-Stiftung [2005.133.2]
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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 T-reg 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 T-reg cells. Therefore, we studied whether polyclonal in vitro prestimulation of conventional, that is T-reg-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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