BONE-MARROW AND PERIPHERAL-BLOOD LYMPHOCYTE PHENOTYPE IN PATIENTS WITH BONE-MARROW FAILURE

Patients with aplastic anemia (AA) respond to immunosuppressive therap y, and several lines of laboratory evidence support a role for cell-me diated immunity in the pathogenesis of marrow failure including expans ion of cytotoxic T lymphocytes (CTL) in the blood of AA patients, over expression of inhibitors such as IFN-gamma in the marrow of AA patient s, and suppression of hematopoietic cells by CTL in vitro. However, th e phenotype of immune effecters in the marrow of AA patients remains u nknown. We examined severe (sAA) and moderate AA (mAA) patients and co mpared them to healthy volunteers and patients with myelodysplastic sy ndrome (MDS). Our study shows that percentages of HLA-DR(+) CD8(+) lym phocytes and natural killer (NK) cells, CD56(+), were elevated in the marrow of AA patients. Peripheral blood (PB), in all instances, did no t 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 on ly 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 f rom sAA and MDS patients. Percentages of activated immune effecters ar e increased in the marrow of AA patients as is consistent with a local ized immune response in this disease. Marrow phenotyping may be more s ensitive than peripheral blood analysis for detecting an abnormal cell ular immune response.