Clinical relevance of balance between type 1 and type 2 immune responses of lymphocyte subpopulations in aplastic anaemia patients

Summary Immune dysfunction, which leads to the suppression of haemopoiesis by cytokines that are secreted by activated T lymphocytes, is considered to play a key role in the pathogenesis of acquired aplastic anaemia (AAA). We investigated the intracytoplasmic expression of type‐1 [interferon γ (IFN‐γ), interleukin (IL)‐2] and type‐2 (IL‐4, IL‐10) cytokines in CD4+ and CD8+ T cells before and after in vitro activation in 16 patients with AAA and 17 normal controls. Untreated or refractory patients had a significantly higher proportion of unstimulated CD4+ and CD8+ T cells that produced IFN‐γ and IL‐2 whereas the IL‐4 and IL‐10 producing T cells did not differ from that of controls, resulting in a shift of IFN‐γ/IL‐4 ratio towards a type‐1 response. Patients in remission had also increased proportion of IFN‐γ‐producing unstimulated CD4+ and CD8+ cells, with a parallel rise of IL‐4‐ and IL‐10‐producing cells and normal IFN‐γ/IL‐4 ratio. These data indicate that, in newly diagnosed and refractory patients with AAA, CD4+ cells are polarized towards a type‐1 response that in turn leads to activation of cytotoxic CD8+ cells and finally to haemopoietic stem cell destruction. The type‐1 response persists in patients in remission although this effect is compensated by the increase of IL‐4 and IL‐10 production.