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 lymphocytes (LGL) from normal individuals and from Felty's syndrome (FS) or LGL syndrome 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 stem cells, and percentage inhibition was calculated. Recombinant chemokines and Fas-stimulating molecules were used in separate cultures to address possible mechanisms of suppression. Proliferation after stimulation with interleukin-2 (IL-2) and anti-CD3 was assessed.


RESULTS
Significant (79%) suppression of colony-forming unit-granulocyte-macrophage (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/Fas ligand interactions or by the chemokines macrophage inhibitory protein 1alpha or IL-8. LGL from both patients and controls were largely CD28- and had reduced proliferative capacity.


CONCLUSIONS
In a subset of FS patients, expansion of CD8+,CD57+ T cells in the bone marrow may be responsible for neutropenia by suppressing neutrophil precursors. This effect is also seen with normal LGL, which are likely to have an important function in neutrophil homeostasis.
Coakley
G
G
Guy's, King's and St. Thomas' Hospitals School of Medicine, London, UK.
Iqbal
M
M
Brooks
D
D
Panayi
G S
GS
Lanchbury
J S
JS
D000368:Aged / Q000502:physiology*; D018959:CD57 Antigens / Q000097:blood*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002455:Cell Division; D005258:Felty Syndrome / Q000150:complications; D005312:Fetal Blood / Q000166:cytology; D006098:Granulocytes / Q000166:cytology; D006801:Humans; D007945:Leukemia, Lymphoid / Q000150:complications; D008264:Macrophages / Q000166:cytology; D009503:Neutropenia / Q000209:etiology; D009504:Neutrophils / Q000166:cytology*; D013234:Stem Cells; D013601:T-Lymphocytes / Q000276:immunology*
D018959:CD57 Antigens