Cytotoxic minor histocompatibility antigen HA-1-specific CD8+ effector memory T cells
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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. / Schilbach, Karin; Kerst, Gunter; Walter, Steffen; Eyrich, Matthias; Wernet, Dorothee; Handgretinger, Rupert; Xie, Weidong; Rammensee, Hans-Georg; Müller, Ingo; Bühring, Hans-Jörg; Niethammer, Dietrich.
In: BLOOD, Vol. 106, No. 1, 01.07.2005, p. 144-9.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Cytotoxic minor histocompatibility antigen HA-1-specific CD8+ effector memory T cells
T2 - artificial APCs pave the way for clinical application by potent primary in vitro induction
AU - Schilbach, Karin
AU - Kerst, Gunter
AU - Walter, Steffen
AU - Eyrich, Matthias
AU - Wernet, Dorothee
AU - Handgretinger, Rupert
AU - Xie, Weidong
AU - Rammensee, Hans-Georg
AU - Müller, Ingo
AU - Bühring, Hans-Jörg
AU - Niethammer, Dietrich
PY - 2005/7/1
Y1 - 2005/7/1
N2 - 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 antibody (Ab) and either high-density (HD) or low-density (LD) major histocompatibility complex (MHC) class I molecules loaded with HA-1(H), a nonapeptide derived from the hematopoiesis-restricted minor histocompatibility antigen HA-1. HD- and LD-aAPCs potently induced HA-1(H)-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 T(c)1 effector memory cells, survived a long time in vitro, and were expanded by a factor varying between 8.2 x 10(4) and 51 x 10(4). The T-cell receptor (TCR) repertoire of HA-1H tetramer-positive CTLs was oligoclonal with a prominent usage of Vbeta6. The TCR repertoire of tetramer-positive CTLs was distinct from and more restricted than that of tetramer-negative cells. These findings indicate that aAPCs are attractive tools for the ex vivo generation of HA-1H-specific CTLs suitable for immunotherapy of relapsed leukemia.
AB - 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 antibody (Ab) and either high-density (HD) or low-density (LD) major histocompatibility complex (MHC) class I molecules loaded with HA-1(H), a nonapeptide derived from the hematopoiesis-restricted minor histocompatibility antigen HA-1. HD- and LD-aAPCs potently induced HA-1(H)-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 T(c)1 effector memory cells, survived a long time in vitro, and were expanded by a factor varying between 8.2 x 10(4) and 51 x 10(4). The T-cell receptor (TCR) repertoire of HA-1H tetramer-positive CTLs was oligoclonal with a prominent usage of Vbeta6. The TCR repertoire of tetramer-positive CTLs was distinct from and more restricted than that of tetramer-negative cells. These findings indicate that aAPCs are attractive tools for the ex vivo generation of HA-1H-specific CTLs suitable for immunotherapy of relapsed leukemia.
KW - Adoptive Transfer
KW - Antigen-Presenting Cells
KW - B-Lymphocytes
KW - Blood Donors
KW - CD8-Positive T-Lymphocytes
KW - Cell Line, Transformed
KW - Child
KW - Female
KW - Humans
KW - Immunologic Memory
KW - In Vitro Techniques
KW - Male
KW - Minor Histocompatibility Antigens
KW - Oligopeptides
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma
KW - T-Lymphocytes, Cytotoxic
U2 - 10.1182/blood-2004-07-2940
DO - 10.1182/blood-2004-07-2940
M3 - SCORING: Journal article
C2 - 15731181
VL - 106
SP - 144
EP - 149
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 1
ER -