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Characterization of regulatory T cells in patients with B-cell chronic lymphocytic leukemia.

Abstract
The status of the immune system of patients with B-cell chronic lymphocytic leukemia (B-CLL) is not yet sufficiently characterized. Clinically, B-CLL patients present immunodeficiency increasing along with disease progression and signs of autoimmunity. In the current study, we evaluated the expression of FOXP3 in CD4+CD25hi T regulatory lymphocytes (Treg) and their influence on immune response against tumor and viral antigens in the complex system of peripheral blood mononuclear cells. In 80 B-CLL patients, the frequency of Treg (CD4+CD25hi FOXP3+) cells was significantly higher in B-CLL patients when compared to healthy volunteers (HV) and increased with the progression of the disease (median: 8.24% in stage A, 11.24% in stage B and 12.57% in stage C according to the Binet classification). The frequency of Treg showed no correlation with prognostic markers such as ZAP-70, CD38 and HLA-G. Notably, Treg frequency correlated with serum levels of TNF (r(2)=0.45, p=0.001). T-cell immune responses against epitopes derived from the tumor-associated antigens survivin, fibromodulin and RHAMM as well as from the influenza matrix protein were evaluated. Functionally, higher frequencies of Treg correlated with decreased T-cell responses against viral and tumor antigens. In conclusion, we detected higher frequencies of Treg in B-CLL patients than in HV. Furthermore, Treg constitute the crucial mechanism of immunosuppression in B-CLL patients.
AuthorsKrzysztof Giannopoulos, Michael Schmitt, Malgorzata Kowal, Paulina Wlasiuk, Agnieszka Bojarska-Junak, Jinfei Chen, Jacek Rolinski, Anna Dmoszynska
JournalOncology reports (Oncol Rep) Vol. 20 Issue 3 Pg. 677-82 (Sep 2008) ISSN: 1021-335X [Print] Greece
PMID18695923 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Peptide Fragments
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Interferon-gamma
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • CD4-Positive T-Lymphocytes (immunology, pathology)
  • Female
  • Forkhead Transcription Factors (metabolism)
  • Humans
  • Interferon-gamma (metabolism)
  • Leukemia, Lymphocytic, Chronic, B-Cell (immunology, metabolism, pathology)
  • Male
  • Middle Aged
  • Peptide Fragments (metabolism)
  • Prognosis
  • Receptors, Tumor Necrosis Factor, Type I (metabolism)
  • Receptors, Tumor Necrosis Factor, Type II (metabolism)
  • T-Lymphocytes, Regulatory (immunology, metabolism, pathology)
  • ZAP-70 Protein-Tyrosine Kinase (metabolism)

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