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 Blood, 12 November 2009, Vol. 114, No. 20, pp. 4575-4582.
Prepublished online as a Blood First Edition Paper on August 31, 2009; DOI 10.1182/blood-2009-04-218248.

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TRANSPLANTATION

Superagonistic CD28 stimulation of allogeneic T cells protects from acute graft-versus-host disease

Niklas Beyersdorf1, Xin Ding1, Thomas Hünig1, and Thomas Kerkau1

1 University of Würzburg, Institute for Virology and Immunobiology, Würzburg, Germany

Acute graft-versus-host disease (aGVHD) often precludes successful immunotherapy of hematologic malignancies with allogeneic T cells. Therefore, we investigated the effect of immunomodulatory superagonistic anti-CD28 monoclonal antibodies (CD28-SA) on the capacity of allogeneic T cells to mediate both aGVHD and the protective graft-versus-tumor (GVT) response. In vivo pretreatment of donor C57BL/6 mice or short-term in vitro culture of donor lymph node cells with a CD28-SA efficiently protected BALB/c recipient mice from aGVHD. This protection strongly relied on the presence of CD28-SA–activated CD4+ CD25+ Foxp3+ regulatory T cells in the donor T-cell inoculum. With respect to the GVT response, CD28-SA–prestimulated T cells were still as potent in clearing lymphoma cells as were T cells without CD28-SA preactivation. Taken together, our data suggest that CD28-SA stimulation of bulk leukocyte cultures in vitro markedly increases the therapeutic window for adoptive immunotherapy with allogeneic T cells in vivo.


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