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

  1. 1Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
  2. 2Department of Pediatrics, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
  3. 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.

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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-italic gamma 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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