Analysis of the expression of critical activation/interaction markers on peripheral blood T cells in B-cell chronic lymphocytic leukaemia: evidence of immune dysregulation.
B-cell chronic lymphocytic leukaemia (B-CLL) is characterized by an accumulation of clonal malignant B cells. The intrinsic characteristics that permit this accumulation have been extensively studied and described. However, it is possible that proliferation and survival of this malignant clone is facilitated by a disruption in the interaction between B and T cells that normally regulate the immune system. In this study, using flow cytometry and cell culture techniques, marked abnormalities of the expression of certain key activation and interaction molecules on the peripheral blood T cells of patients with B-CLL were demonstrated. In particular, on comparison with normal controls, there was a marked reduction in the number of circulating T cells expressing CD25 (interleukin 2 receptor) (P = 0.007), CD28 (P = 0.01) and CD152 (CTLA-4) (P = 0.001). There was also a reduction in the number of circulating T cells expressing CD4 (P = 0.03), CD5 (P = 0.05) and CD11a (P = 0.01). There was no difference in the number expressing T-cell receptor alphabeta (P = 0.1), CD8 (P = 0.4), CD54 (P = 0.4) and CD154 (P = 0.5), and the only marker expressed on a greater number of circulating T cells in B-CLL patients was HLA-DR (P = 0.05). These results suggest that there is a profound T-cell dysregulation that may contribute to the survival of the malignant B cells in patients with B-CLL and to the related autoimmune phenomena of the disease.
Scrivener
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Derriford Combined Laboratory, Derriford Hospital, Plymouth, Devon PL6 8DH, UK. sophie.scrivener@phnt.swest.nhs.uk
Kaminski
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ER
Demaine
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Prentice
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D000069594:Abatacept; D015703:Antigens, CD / Q000032:analysis*; D000943:Antigens, Differentiation / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D018106:CD28 Antigens / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D018956:CD5 Antigens / Q000032:analysis; D060908:CTLA-4 Antigen; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D018796:Immunoconjugates; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015415:Biomarkers; D018106:CD28 Antigens; D015704:CD4 Antigens; D018956:CD5 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006684:HLA-DR Antigens; D018796:Immunoconjugates; D016169:Lymphocyte Function-Associated Antigen-1; D015375:Receptors, Interleukin-2; D000069594:Abatacept