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Expression of P2X5 in lymphoid malignancies results in LRH‐1‐specific cytotoxic T‐cell‐mediated lysis
Author(s) -
Overes Ingrid M.,
De Rijke Björn,
Van HorssenZoetbrood Agnes,
Fredrix Hanny,
De Graaf Aniek O.,
Jansen Joop H.,
Van Krieken J. Han J. M.,
Raymakers Reinier A. P.,
Van Der Voort Robbert,
De Witte Theo M.,
Dolstra Harry
Publication year - 2008
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2008.07125.x
Subject(s) - ctl* , cytotoxic t cell , immunology , biology , immunotherapy , haematopoiesis , transplantation , minor histocompatibility antigen , t cell , cancer research , cd8 , immune system , stem cell , medicine , major histocompatibility complex , microbiology and biotechnology , genetics , in vitro
Summary Minor histocompatibility antigens (MiHA) selectively expressed by haematopoietic cells are attractive targets for specific immunotherapy after allogeneic stem cell transplantation (SCT). Previously, we described LRH‐1 as a haematopoietic‐lineage restricted MiHA that is capable of eliciting an allogeneic cytotoxic T‐lymphocyte (CTL) response after SCT and donor lymphocyte infusion. Importantly, the gene encoding LRH‐1, P2X5, is not expressed in prominent graft‐versus‐host‐disease target tissues such as skin, liver and gut. Here, we investigate whether LRH‐1‐specific immunotherapy may be exploited for the treatment of lymphoid malignancies. We examined P2X5 mRNA expression in a large panel of patient samples and cell lines from different types of lymphoid malignancies by real‐time quantitative reverse transcription polymerase chain reaction. P2X5 mRNA was highly expressed in malignant cells from all stages of lymphoid development. Furthermore, all LRH‐1‐positive lymphoid tumour cell lines were susceptible to LRH‐1 CTL‐mediated lysis in flow cytometry‐based cytotoxicity assays. However, interferon‐γ production was low or absent after stimulation with some cell lines, possibly due to differences in activation thresholds for CTL effector functions. Importantly, primary cells from patients with lymphoid malignancies were effectively lysed by LRH‐1‐specific CTL. These findings indicate that MiHA LRH‐1 is a potential therapeutic target for cellular immunotherapy of lymphoid malignancies.