REGULATION OF INTERLEUKIN-4 PRODUCTION AND CYTOKINE-INDUCED GROWTH-POTENTIAL IN PERIPHERAL T-CELL NON-HODGKINS-LYMPHOMAS

The malignant cells in tumour tissues produce cytokines/growth factors that may influence tumour growth, tumour immunogenicity and host immu ne response, We demonstrate that lymph node cell (LNC) purified neopla stic T cells from CD4(+) peripheral T-cell lymphoma (CD4(+) PTCL) and CD8(+) PTCL spontaneously and after stimulation with anti-CD3, secrete d high amounts of interleukin-4 (IL-4) as compared to LNC-purified CD4 (+) and CD8(+) non-malignant T cells. Furthermore, IL-4 was observed t o be the most potent cytokine that induced in vitro proliferation and growth of the malignant T cells. Moreover, malignant T-cell-derived IL -4 secretion was augmented by exogeneous recombinant human interferon- gamma (IFN-gamma) and was profoundly inhibited by IL-2. Because IL-4 w as shown to be a locally active cytokine with a wide range of immunore gulatory properties, regulation of IL-2 production by IFN-gamma and IL -2 in malignant T cells may be one of the important parameters to be a ssessed in the design of anticancer-specific immunotherapy. In summary we report that malignant T cells produce IL-4, a type 2 cytokine (Th2 cell response) that acts as a growth factor and which may play a crit ical role in PTCL disease mechanism.