Expansion of CD4+ T cells with a cytotoxic phenotype in patients with B-chronic lymphocytic leukaemia (B-CLL).
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.
Porakishvili
N
N
Department of Immunology & Molecular Pathology, Royal Free and Middlesex Hospital Medical School, London, UK. n_porakishvili@hotmail.com
Roschupkina
T
T
Kalber
T
T
Jewell
A P
AP
Patterson
K
K
Yong
K
K
Lydyard
P M
PM
D000368:Aged; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000145:classification* / Q000201:enzymology / Q000276:immunology*; D018959:CD57 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D004950:Esterases / Q000378:metabolism; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016176:T-Lymphocyte Subsets / Q000145:classification; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification* / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D018959:CD57 Antigens; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D015847:Interleukin-4; D007371:Interferon-gamma; D004950:Esterases; C022635:serine esterase