Expansion of CD4+ T cells with a cytotoxic phenotype in patients with B-chronic lymphocytic leukaemia (B-CLL)

Clin Exp Immunol. 2001 Oct;126(1):29-36. doi: 10.1046/j.1365-2249.2001.01639.x.

Abstract

Abnormal CD4/CD8 ratios and T-cell function have previously been shown in patients with B-chronic lymphocytic leukaemia (B-CLL). We have demonstrated that CD4+ T cells containing both serine esterase and perforin (PF) are increased in the blood of these patients. Using flow cytometry, we have shown that the CD4+ PF+ cells were CD57+ but lacked expression of CD28, suggesting a mature population. The same phenotype in CD8+ T cells is characteristic of mature cytotoxic T cells. However, in contrast to the CD8+ T cells, the CD4+ T cells were more frequently CD45RO positive than CD45RA positive, indicating prior antigen experience. In contrast, this population lacked expression of either CD69 or HLA-DR, arguing that they were not activated or that they are an abnormal population of T cells. Their constitutive cytokine levels showed them mainly to contain IL4 and not IFNgamma, suggesting a Th2 phenotype. The role of the CD4+ PF+ T-cell population is at present uncertain. However, this potentially cytotoxic T-cell population could contribute both to enhancing survival of the B-CLL tumour cells through production of IL4, and to the immunodeficient state frequently seen in patients with this tumour, independent of drug treatment.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD28 Antigens / metabolism
  • CD4-CD8 Ratio
  • CD4-Positive T-Lymphocytes / classification*
  • CD4-Positive T-Lymphocytes / enzymology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD57 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / immunology
  • Esterases / metabolism
  • Female
  • Humans
  • Immunophenotyping
  • Interferon-gamma / biosynthesis
  • Interleukin-4 / biosynthesis
  • Killer Cells, Natural / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Lymphocyte Activation*
  • Male
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • T-Lymphocyte Subsets / classification
  • T-Lymphocytes, Cytotoxic / classification*
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • CD28 Antigens
  • CD57 Antigens
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Perforin
  • Interleukin-4
  • Interferon-gamma
  • Esterases
  • serine esterase