IL4 production and increased CD30 expression by a unique CD8+ T-cell subset in B-cell chronic lymphocytic leukaemia

Phenotypic and functional abnormalities within the residual non-B-cell compartment of B-cell chronic lymphocytic leukaemia (CLL) suggest an interaction between tumour cells and host immune effectors. To explore the possibility of a polarized Th1/Th2 response we have studied CD30 antigen expression and the pattern of cytokine production by purified CLL T cells. Activated T cells from CLL patients showed a significant increase in the expression of CD30 compared to normal controls. Accordingly, high levels of soluble CD30 were detected in supernatants from activated T-cell cultures, as well as in CLL serum samples. Messenger RNA for IL4 was found in both resting and, to a greater extent, in activated CLL T lymphocytes. The latter cells were also capable of releasing IL4. Three-colour immunofluorescence analyses revealed a strong CD30 expression in the CD3+/CD8+/CD28- large granular lymphocyte subset, which is considerably expanded in CLL. Production of IL4, as well as expression and release of CD30 by these T cells, was conclusively demonstrated at the clonal level. These findings document an expansion of a peculiar subset of 'Th2-like' cells in CLL, with an increased IL4 production and CD30 expression and release, that are likely to contribute to both the B-cell accumulation and immune-defects characteristic of this disease.