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

• Published in: Clinical and experimental immunology Vol. 126; no. 1; pp. 29 - 36
• Main Authors: Porakishvili, N., Roschupkina, T., Kalber, T., Jewell, A. P., Patterson, K., Yong, K., Lydyard, P. M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-10-2001; Blackwell; Blackwell Science Inc
• Subjects: Aged; Antigens, Differentiation, T-Lymphocyte - metabolism; Biological and medical sciences; B‐CLL perforin; Cancer Immunology; CD28 Antigens - metabolism; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes - classification; CD4-Positive T-Lymphocytes - enzymology; CD4-Positive T-Lymphocytes - immunology; CD57; CD57 Antigens - metabolism; CD8-Positive T-Lymphocytes - enzymology; CD8-Positive T-Lymphocytes - immunology; cytotoxic CD4 cells; Esterases - metabolism; Female; Hematologic and hematopoietic diseases; Humans; Immunophenotyping; Interferon-gamma - biosynthesis; Interleukin-4 - biosynthesis; Killer Cells, Natural - immunology; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Activation; Male; Medical sciences; Membrane Glycoproteins - metabolism; Middle Aged; Perforin; Pore Forming Cytotoxic Proteins; serine esterase; T-Lymphocyte Subsets - classification; T-Lymphocytes, Cytotoxic - classification; T-Lymphocytes, Cytotoxic - immunology; Human; Immune response; Immunophenotype; Enzyme; Cytokine; Malignant hemopathy; Esterases; Cellular immunity; B-Lymphocyte; Cell subpopulation; Chronic; Interleukin 4; Chronic lymphocytic leukemia; Lymphoproliferative syndrome; T-Lymphocyte; Hydrolases; Th2 lymphocyte; Perforin; Cytotoxic T lymphocyte
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.2001.01639.x

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 IFNγ, 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.