T cell-mediated inhibition of erythropoiesis in aplastic anaemia: the possible role of IFN-gamma and TNF-alpha.
The inhibitory activity of T cells on autologous erythroid colony-forming units (CFU-E) (T cell inhibitory activity) in patients with aplastic anaemia (AA) was investigated. In 11 (32.4%) out of 34 AA cases, T cell inhibition on autologous CFU-E growth was greater than that in normal individuals. In order to evaluate the mechanism of this inhibitory activity, T cell surface markers, interferon (IFN) production in peripheral blood mononuclear cell (PBMNC) liquid culture, and cytokine levels such as IFN and tumour necrosis factor-alpha (TNF-alpha) in CFU-E clot cocultured with T cells, were measured in a portion of the patients. In five patients investigated for IFN production in PBMNC liquid culture, all produced statistically more IFN activity than normal individuals under phytohaemagglutinin (PHA-P) stimulation (P less than 0.01) with no relation to T cell inhibitory activity. In only one patient whose T cells displayed increased CD8 and HLA-DR antigen (CD8+HLA-DR+) and inhibitory activity, a significant amount of IFN-gamma was observed in CFU-E clot cocultured with T cells, and the addition of anti-IFN-gamma antibody to the coculture resulted in recovered CFU-E colony growth. These results suggest that IFN-gamma production by T cells may explain, at least in part, the pathogenesis of haematopoietic defects in AA. In other patients however, T cell inhibitory activity neither correlated to the T cell subpopulations (CD4+/CD8+, CD8+HLA-DR+), IFN production in PBMNC liquid culture, nor to IFN and TNF-alpha levels in CFU-E clot culture. The roles played by cytokines other than IFN and TNF-alpha on haematopoietic precursor cells require further evaluation in a larger sample of patients with AA.
Miura
A
A
Department of Internal Medicine, National Sendai Hospital, Japan.
Endo
K
K
Sugawara
T
T
Kameoka
J
J
Watanabe
N
N
Meguro
K
K
Fukuhara
O
O
Sato
I
I
Suzuki
C
C
Yoshinaga
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000097:blood / Q000276:immunology*; D015672:Erythroid Precursor Cells / Q000276:immunology; D004920:Erythropoiesis / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma