Beyersdorf Niklas, Werner Sandra, Wolf Nelli, Hünig Thomas, Kerkau Thomas
Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
Eur J Immunol. 2015 Jul;45(7):1997-2007. doi: 10.1002/eji.201445317. Epub 2015 May 12.
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.
将来自经CD28超激动剂（CD28-SA）处理的供体的T细胞移植到经辐照的同种异体宿主中时，CD28-SA诱导的调节性T细胞（Treg细胞）活化和扩增可抑制急性移植物抗宿主病（aGvHD），同时又不会消除所需的移植物抗肿瘤效应。然而，人外周血CD4(+) T细胞中仅含有极少数的Treg细胞。因此，我们研究了用包被有CD28-SA的顺磁珠对C57BL/6小鼠的常规（即Treg细胞耗竭的）CD4(+) T细胞进行多克隆体外预刺激，是否足以保护受体BALB/c小鼠免受aGvHD的影响。对常规CD4(+) T细胞进行CD28-SA预刺激可有效保护BALB/c受体小鼠免受aGvHD的影响，并且经CD28-SA刺激的CD4(+)和CD8(+) T细胞能够介导对BCL1淋巴瘤的长期保护。最近完成的人CD28-SA TGN1412/TAB08的成功I期试验应会极大地促进将这种直接方法进一步开发成一种针对患者的新型免疫疗法。
