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‐...

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Bibliographic Details
Published in:British journal of haematology 2004-01, Vol.124 (1), p.97-105
Main Authors: Giannakoulas, Nikolaos C., Karakantza, Marina, Theodorou, Georgios L., Pagoni, Maria, Galanopoulos, Athanasios, Kakagianni, Theodora, Kouraklis‐Symeonidis, Alexandra, Matsouka, Panagiota, Maniatis, Alice, Zoumbos, Nicholas C.
Format: Article
Language:English
Subjects:
Adult
Aged
Anemia, Aplastic - immunology
aplastic anaemia
Biological and medical sciences
CD4+ cells
CD8+ cells
Cytoplasm - immunology
Female
Hematologic and hematopoietic diseases
Hematology
Humans
Immunophenotyping
interferon γ
Interferon-gamma - metabolism
Interleukin-10 - metabolism
Interleukin-2 - metabolism
Interleukin-4 - metabolism
Interleukins - metabolism
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Male
Medical sciences
Middle Aged
T-Lymphocyte Subsets - immunology
Th1 Cells - immunology
Th2 Cells - immunology
type‐1/type‐2 cytokines
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Summary: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.
ISSN:0007-1048
1365-2141
DOI:10.1046/j.1365-2141.2003.04729.x