T‐Lymphocyte Functions in Acute Leukaemia Patients with Severe Chemotherapy‐Induced Cytopenia: Characterization of Clonogenic T‐Cell Proliferation

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Abstract
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.