title: GPI-anchored protein-deficient T cells in patients with aplastic anemia and low-risk myelodysplastic syndrome: implications for the immunopathophysiology of bone marrow failure.
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 CD48(-) CD59(-) CD3(+) 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 CD48(-) CD59(-) CD3(+) 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 CD48(-) CD59(-) T cells consisted of predominantly effector memory (EM) and terminal effector cells, while CD48(-) CD59(-) 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.
authors.affiliation: Clinical Laboratory Science, Division of Health Sciences, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Katagiri
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Qi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ohtake
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000276:immunology / Q000378:metabolism*; D001855:Bone Marrow Diseases; D000080983:Bone Marrow Failure Disorders; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D058851:GPI-Linked Proteins / Q000172:deficiency* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D016130:Immunophenotyping; D066298:In Vitro Techniques; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology / Q000378:metabolism*; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000494:pharmacology; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D055815:Young Adult
chemical_list: D058851:GPI-Linked Proteins; D008565:Membrane Proteins; D053240:Receptors, Tumor Necrosis Factor, Member 14; C506028:TNFRSF14 protein, human; D016212:Transforming Growth Factor beta; C080086:phosphatidylinositol glycan-class A protein