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Impaired expression of the CD3-zeta chain in peripheral blood T cells of patients with chronic myeloid leukaemia results in an increased susceptibility to apoptosis. Br J Haematol 2000 Dec;111(3):817-25

Date

12/21/2000

Pubmed ID

11122143

DOI

10.1046/j.1365-2141.2000.02415.x

Scopus ID

2-s2.0-0034494607   52 Citations

Abstract

In patients with myeloid malignancies, cell-mediated immunity is often suppressed, being most profound in those with advanced disease. Such immune dysfunction, as demonstrated in many patients with chronic lymphocytic leukaemia (CLL) and myelodysplastic syndrome (MDS), may, at least in part, be due to altered expression of the CD3-zeta chain, which is an important component of the T-cell receptor (TCR). We speculated that impaired expression of the TCR-zeta chain would be evident in peripheral blood T cells of patients with chronic myeloid leukaemia (CML) and that such an abnormality would result in an increased ex vivo susceptibility to apoptosis. In this study, we demonstrated that, compared with normal controls, zeta chain expression was significantly downregulated in all of the T-cell subsets (P < 0.009) in more than 90% of CML patients. In addition, there was a significantly lower expression of the CD3-epsilon chain (P < 0.001) in patients than in controls. In those patients with abnormal zeta chain expression, the proportion of lymphocytes with spontaneous DNA fragmentation, as determined by terminal deoxynucleotide transferase-mediated dUTP-biotin nick-end labelling (TUNEL) assays, was also significantly higher (P < 0.002) than controls. From all of the patients tested, it was possible to upregulate partially zeta chain expression and hence to reduce the susceptibility to apoptosis by cross-linking the T cells with interleukin (IL)-2, interferon (IFN)-alpha or immobilized CD3. In addition, such cross-linked T cells showed a significantly higher capacity to proliferate than the native CML T cells.

Author List

Chen X, Woiciechowsky A, Raffegerst S, Schendel D, Kolb HJ, Roskrow M

Author

Xiao Chen MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Apoptosis
CD3 Complex
CD4-Positive T-Lymphocytes
CD56 Antigen
CD8-Positive T-Lymphocytes
Cell Division
Cross-Linking Reagents
Flow Cytometry
Gene Expression
Gene Rearrangement, T-Lymphocyte
Humans
Immunoglobulin epsilon-Chains
In Situ Nick-End Labeling
Interferon-alpha
Interleukin-2
Killer Cells, Natural
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Middle Aged
Receptor-CD3 Complex, Antigen, T-Cell
T-Lymphocytes