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Blood, 1 July 2005, Vol. 106, No. 1, pp. 144-149.
Prepublished online as a Blood First Edition Paper on February 24, 2005; DOI 10.1182/blood-2004-07-2940.
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Submitted July 29, 2004
Accepted February 11, 2005
Cytotoxic minor histocompatibility antigen HA-1-specific CD8+ effector memory T cells: Artificial APCs pave the way for clinical application by potent primary in vitro induction
Karin Schilbach*, Gunter Kerst, Steffen Walter, Matthias Eyrich, Dorothee Wernet, Rupert Handgretinger, Weidong Xie, Hans-Georg Rammensee, Ingo Muller, Hans-Jorg Buhring, and Dietrich Niethammer
University Children's Hospital Tubingen, Tubingen, Germany
Department of Immunology, Institute for Cell Biology, University of Tubingen, Tubingen, Germany
Department of Transfusion Medicine, University Hospital Tubingen, Tubingen, Germany
St. Jude Children's Research Hospital, Memphis, TN, USA
Department of Hematology and Oncology, University Hospital Tubingen, Tubingen, Germany
* Corresponding author; email: knschilb{at}med.uni-tuebingen.de.
Induction of cytotoxic T lymphocytes (CTLs) for treatment of relapsed leukemia after allogeneic stem cell transplantation is hindered by the laborious and time-consuming procedure of generating dendritic cells for antigen presentation. Artificial antigen-presenting cells (aAPCs) offer the advantage of being readily available in sufficient numbers, thus allowing for a highly standardized in vitro induction of CTLs. We generated aAPCs coated with anti-CD28-Ab and either high-density (HD) or low-density (LD) MHC class I molecules loaded with a nonapeptide derived from the hematopoiesis-restricted minor histocompatibility antigen HA-1H. HD- and LD-aAPCs potently induced HA-1H-specific CD8+ CTLs from untouched CD8+ T cells of healthy donors. CTLs were subsequently purified by magnetic activated cell sorting. HD- as well as LD-aAPC-induced CTLs exerted high HA-1H-specific cytotoxicity, resembled Tc1 effector memory cells, survived long time in vitro and were expanded by a factor varying between 8.2 and 51x104. T-cell receptor (TCR) repertoire of HA-1-tetramer+ CTLs was oligoclonal with a prominent usage of V 6. The TCR repertoire of tetramer+ CTLs was distinct from and more restricted than that of tetramer- cells. These findings indicate that aAPCs are attractive tools for the ex vivo generation of HA-1-specific CTLs suitable for immunotherapy of relapsed leukemia.

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