CD8+,CD57+T cells from healthy elderly subjects suppress neutrophil development in vitro - Implications for the neutropenia of Felty's and large granular lymphocyte syndromes

Objective. To investigate the ability of CD8+,CD57+ large granular lymphocy tes (LGL) from normal individuals and from Felty's syndrome (FS) or LGL syn drome patients to suppress allogeneic neutrophil precursor development. Methods. Six FS patients, 5 LGL syndrome patients, and 13 elderly controls were studied, CD8+,CD57+ T cells were cocultured with cord blood-derived st em cells, and percentage inhibition was calculated. Recombinant chemokines and Fas-stimulating molecules were used in separate cultures to address pos sible mechanisms of suppression. Proliferation after stimulation with inter leukin-2 (IL-2) and anti-CD3 was assessed. Results. Significant (79%) suppression of colony-forming unit-granulocyte-m acrophage (CFU-GM) by the CD8+,CD57+ subset was shown by 1 FS patient. None of the CD8+,CD57+ cells from LGL syndrome patients had any effect. Six of 13 controls studied showed >40% inhibition of CFU-GM, and all but 2 showed at least some suppression. The suppressive effect was not mediated by Fas/F as ligand interactions or by the chemokines macrophage inhibitory protein 1 alpha or IL-8, LGL from both patients and controls were largely CD28- and had reduced proliferative capacity. Conclusion. In a subset of FS patients, expansion of CD8+,CD57+ T cells in the bone marrow may be responsible for neutropenia by suppressing neutrophi l precursors, This effect is also seen with normal LGL, which are likely to have an important function in neutrophil homeostasis.