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T‐Lymphocyte Functions in Acute Leukaemia Patients with Severe Chemotherapy‐Induced Cytopenia: Characterization of Clonogenic T‐Cell Proliferation
Author(s) -
Bruserud,
Ulvestad,
Berentsen,
Bergheim,
Nesthus
Publication year - 1998
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1998.00254.x
Subject(s) - cytopenia , clonogenic assay , chemotherapy , medicine , immunology , cancer research , lymphocyte , oncology , biology , cell , bone marrow , genetics
Intensive chemotherapy for acute leukaemia is followed by a period of severe chemotherapy‐induced leukopenia. We used a limiting dilution assay to investigate whether remaining CD4 + and CD8 + T lymphocytes derived from such leukopenic patients could be activated and undergo clonogenic proliferation. The activation signal in our model was accessory cells (irradiated normal peripheral blood mononuclear cells) + phytohaemagglutinin (PHA) + interleukin‐2 (IL‐2). During severe leukopenia a majority of circulating lymphocytes were CD4 + T cells. Clonogenic proliferating T lymphocytes were detected for all patients. Higher frequencies of clonogenic cells were detected in the CD8 + subset as compared to the CD4 + subset. However, for both subsets frequencies of proliferating cells were decreased compared with healthy individuals. The CD4 + and CD8 + lymphocytes were also capable of proliferation in response to alloactivation, and accessory cells mainly containing acute myelogenous leukaemia blast were efficient as accessory cells for activation. For the CD4 + cells, increased proliferation was detected in the presence of acute myelogenous leukaemia (AML) blasts compared with normal accessory cells. Based on our results we conclude that: (1) although acute leukaemia patients with therapy‐induced leukopenia have both a quantitative and a qualitative T‐cell defect, (2) the remaining T‐cell population includes a subset capable of clonogenic proliferation. However, (3) proliferation of the clonogenic CD4 + cells can be modulated by AML blasts.