In vitro polyclonal activation of conventional T cells with a CD28 superagonist protects mice from acute graft versus host disease.

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.

journal_name

Eur J Immunol

authors

Beyersdorf N,Werner S,Wolf N,Hünig T,Kerkau T

doi

10.1002/eji.201445317

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

1997-2007

issue

7

eissn

0014-2980

issn

1521-4141

journal_volume

45

pub_type

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