Graft-Versus-Tumor Effects
Bone Marrow Transplantation (2004) 34, 703–709. doi:10.1038/sj.bmt.1704583 Published online 23 August 2004
Expansion and activation of minor histocompatibility antigen HY-specific T cells associated with graft-versus-leukemia response
A Takami1, C Sugimori1, X Feng1, A Yachie2, Y Kondo1, R Nishimura2, K Kuzushima3, T Kotani1, H Asakura1, S Shiobara1 and S Nakao1
- 1Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
- 2Department of Pediatrics, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
- 3Laboratory of Viral Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan
Correspondence: Dr A Takami, Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, 13-1 Takaramachi, Kanazawa 920-8641, Japan. E-mail: takami@med3.m.kanazawa-u.ac.jp
Received 20 October 2003; Accepted 13 April 2004; Published online 23 August 2004.
Abstract
The immune system of females is capable of recognizing and reacting against the male-specific minor histocompatibility antigen (mHA), HY. Thus, cytotoxic T-lymphocytes (CTLs) recognizing this antigen may be useful in eradicating leukemic cells of a male patient if they can be generated in vivo or in vitro from a human leukocyte antigen (HLA)-identical female donor. The HLA-A*0201-restricted HY antigen, FIDSYICQV, is a male-specific mHA. Using HLA-A2/HY peptide tetrameric complexes, we reveal a close association between the emergence of HY peptide-specific CD8+ T cells in peripheral blood and molecular remission of relapsed BCR/ABL+ chronic myelogenous leukemia in lymphoid blast crisis in a patient who underwent female-to-male transplantation. Assessment of intracellular cytokine levels identified T cells that produce interferon-
in response to the HY peptide during the presence of HY tetramer-positive T cells. These results indicate that transplant with allogeneic HY-specific CTLs has therapeutic potential for relapsed leukemia, and that expansion of such T cells may be involved in the development of a graft-versus-leukemia response against lymphoblastic leukemia cells.
Keywords:
minor histocompatibility antigen, HY, cytotoxic T-lymphocytes
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