GPI-anchored protein-deficient T cells in patients with aplastic anemia and low-risk myelodysplastic syndrome: implications for the immunopathophysiology of bone marrow failure

Authors

  • Takamasa Katagiri,

    1. Clinical Laboratory Science, Division of Health Sciences
    2. Cellular Transplantation Biology, Division of Cancer Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan
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  • Zhirong Qi,

    1. Cellular Transplantation Biology, Division of Cancer Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan
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  • Shigeki Ohtake,

    1. Clinical Laboratory Science, Division of Health Sciences
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  • Shinji Nakao

    1. Cellular Transplantation Biology, Division of Cancer Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan
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Shinji Nakao, Cellular Transplantation Biology, Division of Cancer Medicine, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi Kanazawa, Ishikawa, Japan. Tel: +81 762 652 274; Fax: +81 762 34 4252; e-mail:snakao@med3.m.kanazawa-u.ac.jp

Abstract

Glycosylphosphatidylinositol-anchored protein-deficient (GPI-AP) T cells can be detected in some patients with bone marrow failure (BMF), but the link between these cells and BMF pathophysiology remains to be elucidated. To clarify the significance of GPI-AP T cells in BMF, peripheral blood from 562 patients was examined for the presence of CD48CD59CD3+ cells using high-resolution flow cytometry (FCM), and the GPI-AP T cells were characterized with regard to their phenotype and sensitivity to inhibitory molecules, including herpesvirus entry mediator (HVEM) and a myelosuppressive cytokine, TGF-β. A multi-lineage FCM analysis detected CD48CD59CD3+ T cells in 72 (12.8%) of the patients, together with GPI-AP myeloid cells. Unexpectedly, 12 patients (10 with aplastic anemia and 2 with myelodysplastic syndrome-refractory anemia, 2.1%), who showed clinical features similar to those of other BMF patients with GPI-AP myeloid cells, such as a good response to immunosuppressive therapy, displayed 0.01–0.3% GPI-AP cells exclusively in T cells. The CD48CD59 T cells consisted of predominantly effector memory (EM) and terminal effector cells, while CD48CD59 T cells from non-BMF patients who had received anti-CD52 antibody only showed EM and central memory phenotypes. TGF-β and HVEM capable of inhibiting T-cell proliferation via its GPI-AP CD160 ligation suppressed the in vitro proliferation of GPI-AP+ T cells more potently than that of GPI-AP T cells from the same patients. The presence of GPI-AP T cells, as well as GPI-AP myeloid cells, may therefore reflect the immunopathophysiology of BMF in which cytokine-mediated suppression of hematopoietic stem cells via GPI-AP-type receptors takes place.

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