Intracellular Cytokines Produced by Stimulated CD3+ Cells from Chronic Myeloid Leukemia Patients

Abstract

Our work examined the production of intracellular interferon (INF)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, and IL-4 by in vitro stimulated CD3+ cells from 38 chronic myeloid leukemia (CML) patients. At the time of diagnosis the percentages of cells producing INF-γ, TNF-α, and IL-2 were strongly suppressed compared to those in healthy control subjects. Hematological remission achieved through treatment with tyrosine-kinase inhibitors was associated with a highly significant increase in the ratio of cells producing all 4 cytokines. The percentages of CD3+ cells producing cytokines were dependent on age, more so in CML patients than in healthy controls, and they negatively correlated with the number of leukocytes. Patients with an optimal therapy outcome possessed higher percentages of cytokine-producing CD3+ cells at diagnosis than those with nonoptimal outcomes. This difference was statistically significant in the case of INF-γ-producing cells, and it was on the brink of significance in the case of IL-2-producing cells.

The dynamic of TNF and IL6 gene expression in chronic myeloid leukemia patients reveals early responders to imatinib

“…1A). Our findings are in agreement with a previous report that demonstrated a strongly suppression of CD3+ cells producing TNF-α and INF-γ in whole blood samples of newly diagnosed CML patients [15]. Also, several studies have shown that NK-cell proportions among lymphocytes were decreased [11], and that T cells were functionally impaired displaying a decreased TCRζ-chain expression, a limited cytotoxic activity and a diminished production of Th1-cytokines (i.e.…”

“…Hematological remission was associated with a highly significant increase of CD3+ cells producing pro-inflammatory Th1 cytokines (i.e. INF-γ and TNF-α) [15] and this T cell response is sustained over time while in remission [12]. Also, patients with a complete cytogenetic response tend to a greater NK-cell reactivity [17].…”

Cytokine Syntheses by T-Cell Subsets From Chronic Myeloid Leukemia Patients: Relationship Between Pre-Treatment Levels and Response to Imatinib Therapy

“…However, data regarding the immune response of autologous T-cell from CML patients were contradicting. Some of the published data reported: 1) decreased in percentage Th1 and tumor necrosis factor (TNF)-α but increase in percentage of Th2 cytokine producing T cells [6][7][8]; 2) decreased in percentage of Th1 and TNF-α but comparable Th2 percentage of cytokine producing T cells [9]; or 3) decrease in percentage of both Th1 And Th2 of cytokine producing T cells from patients with untreated chronic phase CML [10,11]. Although Kiani et al [12] reported normal intrinsic Th1/Th2 balance secreted from purified CD4 T cells from patients with CP CML, they ruled out the presence of intrinsic T-cell defects.…”