title: Bone marrow and peripheral blood lymphocyte phenotype in patients with bone marrow failure.
abstract: Patients with aplastic anemia (AA) respond to immunosuppressive therapy, and several lines of laboratory evidence support a role for cell-mediated immunity in the pathogenesis of marrow failure including expansion of cytotoxic T lymphocytes (CTL) in the blood of AA patients, overexpression of inhibitors such as IFN-gamma in the marrow of AA patients, and suppression of hematopoietic cells by CTL in vitro. However, the phenotype of immune effectors in the marrow of AA patients remains unknown. We examined severe (sAA) and moderate AA (mAA) patients and compared them to healthy volunteers and patients with myelodysplastic syndrome (MDS). Our study shows that percentages of HLA-DR+ CD8+ lymphocytes and natural killer (NK) cells, CD56+, were elevated in the marrow of AA patients. Peripheral blood (PB), in all instances, did not reflect changes seen in the bone marrow (BM). Increased percentages of activated CD8+ cells were found in marrow and blood in 43% of AA patients, but in 28% of AA patients, activation of CD8+ cells was only detectable in the marrow. During hematopoietic recovery, activated CD8+ cells and NK cells in marrow declined, but not to normal levels. T cells bearing the gamma delta-phenotype were elevated in the blood of sAA patients (p < 0.05) but were not significantly increased in BM from sAA and MDS patients. Percentages of activated immune effectors are increased in the marrow of AA patients as is consistent with a localized immune response in this disease. Marrow phenotyping may be more sensitive than peripheral blood analysis for detecting an abnormal cellular immune response.
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: J P
authors.initials: JP
authors.lastname: Maciejewski
authors.forename: J R
authors.initials: JR
authors.lastname: Hibbs
authors.forename: S
authors.initials: S
authors.lastname: Anderson
authors.forename: P
authors.initials: P
authors.lastname: Katevas
authors.forename: N S
authors.initials: NS
authors.lastname: Young
mesh_terms: D000741:Anemia, Aplastic / Q000473:pathology*; D001854:Bone Marrow Cells; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology*; D009190:Myelodysplastic Syndromes / Q000473:pathology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta