Journal of Rafsanjan University of Medical Sciences

  High level of CMV-specific CD4⁺ and CD8⁺cells Immune Response and Correlation Between them in B-cell Chronic Lymphocytic Leukemia Patients 

  B. Pourgheysri [1] , P. Moss [2]

  Received: 10/09/07 Sent for Revision: 05/03/08 Received Revised Manuscript: 06/12/08 Accepted: 30/12/08

  Background and Objective: Chronic lymphocytic leukemia (CLL) is characterized by a monoclonal proliferation of lymphocytes mainly B cells (B-CLL) in the blood and bone marrow. Morphological and functional abnormalities of T cells and monoclonality of them have been documented in CLL. Such expanded cells may be specific for recognition of pathogens. Cytomegalovirus (CMV) is most likely involved in this phenomenon in CLL. CMV infection causes a high level of immune response in immunodeficient patients. In this study, the association between expanded T cells and the immune responses of CMV-specific CD4⁺ and CD8⁺ cells in B-CLL was investigated.

  Matherials and Methods : This was a cross sectional study and the study group were 41 CMV seropositive B-CLL patients and 35 CMV seropositive healthy donors (control group). The level of CMV-specific CD4⁺ and CD8⁺ cells immune responses were detected by intracellular cytokine response to antigenic activation and CMV tetramer respectively.

  Results: The level of CMV-specific CD4⁺ cells responses was significantly higher in patients with a median of 10.99% and 11% for IFN-γ and TNF-α producing CD4+T cells respectively than age-matched controls with a median of 4.3% and 4.6 (p= 0.0004 for IFN-γ and p= 0.003 for TNF-α). The level of CMV-specific CD8⁺ cells immune responses was also higher in patients compared to control group (p= 0.03 for NLV). There was a positive correlation between the level of CD4⁺ and CD8⁺ cells immune responses (p=0.009).

  Conclusions : These results show the deep influence of CMV infection and the immune response to it in T-cell alteration in CLL patients. The increased level of CMV-specific T cells may be the cause of increased level of absolute T cells in these patients.

  Key words : Chronic lymphocytic leukemia, Cytomegalovirus, T-cell, interferon γ, tumor necrosing factor α

  Funding: This work was supported by a scholarship from the Iranian Ministry of Health and Medical Education and UK Molecular Research Centre.

  Conflict of interest: None declared.

  Ethical approval: Approval for this study was obtained from the South Birmingham Local Research Ethics Committee.

  [1] - Assistant Prof., Dept. of Pathology and Hematology, University of Medical Sciences, Shahrekord, Iran

  (Corresponding Author) Tel: (0381)3339941, Fax: (0381)3334911, E-mail: bat238@yahoo.com

  [2] - Prof., Dept. of Hematology, C.R.UK Institute for Cancer Studies, University of Birmingham, Birmingham, England