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 p atients with B-chronic lymphocytic leukaemia (B-CLL). We have demonstrated that CD4(+) T cells containing both serine esterase and perforin (PF) are i ncreased in the blood of these patients. Using flow cytometry, we have show n that the CD4(+) PF+ cells were CD57(+) but lacked expression of CD28, sug gesting a mature population. The same phenotype in CD8(+) T cells is charac teristic 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 act ivated or that they are an abnormal population of T cells. Their constituti ve cytokine levels showed them mainly to contain IL4 and not IFN gamma, sug gesting a Th2 phenotype. The role of the CD4(+) PF+ T-cell population is at present uncertain. However, this potentially cytotoxic T-cell population c ould contribute both to enhancing survival of the B-CLL tumour cells throug h production of IL4, and to the immunodeficient state frequently seen in pa tients with this tumour, independent of drug treatment.