title: Interferon gamma and tumour necrosis factor alpha are overexpressed in bone marrow T lymphocytes from paediatric patients with aplastic anaemia.
abstract: Twelve paediatric patients with aplastic anaemia and two groups of normal control subjects underwent flow cytometric analysis for intracytoplasmic expression of gamma interferon (gamma-IFN) and tumour necrosis factor alpha (TNF-alpha) in bone marrow and peripheral blood CD4+ and CD8+ cells. The same cytokines were tested, by immunoassay, in culture supernatants from unstimulated bone marrow mononuclear cells (MNCs). Marrow CD4+ and CD8+ cells expressing gamma-IFN and TNF-alpha were significantly increased in the patients in comparison with normal control subjects (P from < 0.05 to < 0.0001 in the different cellular subsets). Patients' marrow CD4+ and CD8+ cells containing gamma-IFN and TNF-alpha were significantly increased when compared with the same cell fractions from paired peripheral blood samples (P from < 0.05 to < 0.0001 in the various cellular subsets). In the supernatant of marrow MNCs, gamma-IFN and TNF-alpha were detected in four out of eight and five out of eight cases, respectively, whereas neither cytokine was traceable in the control subjects. Patients' peripheral blood CD4+ and CD8+ cells containing gamma-IFN and TNF-alpha were not significantly increased in comparison with those from normal control subjects. Whereas patients with favourable and unfavourable outcomes had no significantly different proportions of marrow gamma-IFN+/CD4+ and gamma-IFN+/CD8+ cells, the percentages of marrow CD4+ and CD8+ cells containing TNF-alpha were significantly lower in subjects with favourable than in those with unfavourable outcome. Overall, these findings show that, in aplastic patients, T cells overexpressing gamma-IFN and TNF-alpha concentrate in the bone marrow and that intracytoplasmic expression of TNF-alpha in marrow CD4+ and CD8+ cells is associated with an unfavourable clinical course.
authors.affiliation: Department of Paediatric Haematology/Oncology, Scientific Directorate, G. Gaslini Children's Hospital, Largo G. Gaslini 5, 16147 Genoa, Italy. carlodufour@ospedale-gaslini.ge.it
authors.forename: C
authors.initials: C
authors.lastname: Dufour
authors.forename: A
authors.initials: A
authors.lastname: Corcione
authors.forename: J
authors.initials: J
authors.lastname: Svahn
authors.forename: R
authors.initials: R
authors.lastname: Haupt
authors.forename: N
authors.initials: N
authors.lastname: Battilana
authors.forename: V
authors.initials: V
authors.lastname: Pistoia
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003593:Cytoplasm / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma