T cell‐mediated inhibition of erythropoiesis in aplastic anaemia: the possible role of IFN‐γ and TNF‐α

Akira Miura, Kazuyasu Endo, Tomohiro Sugawara, Junichi Kameoka, Norimichi Watanabe, Kuniaki Meguro, Osamu Fukuhara, Isao Sato, Chiyuki Suzuki, Kaoru Yoshinaga

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25 Citations (Scopus)

Abstract

Summary. 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‐α (TNF‐α) 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<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‐γ was observed in CFU‐E clot cocultured with T cells, and the addition of anti‐IFN‐γ antibody to the coculture resulted in recovered CFU‐E colony growth. These results suggest that IFN‐γ 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‐α levels in CFU‐E clot culture. The roles played by cytokines other than IFN and TNF‐α on haematopoietic precursor cells require further evaluation in a larger sample of patients with AA.

Original languageEnglish
Pages (from-to)442-449
Number of pages8
JournalBritish Journal of Haematology
Volume78
Issue number3
DOIs
Publication statusPublished - 1991 Jan 1

ASJC Scopus subject areas

  • Hematology

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