Regulation of interleukin-4 production and cytokine-induced growth potential in peripheral T-cell non-Hodgkin's lymphomas

The malignant cells in tumour tissues produce cytokines/growth factors that may influence tumour growth, tumour immunogenicity and host immune response. We demonstrate that lymph node cell (LNC) purified neoplastic T cells from CD4⁺ peripheral T-cell lymphoma (CD4⁺ PTCL) and CD8⁺ PTCL spontaneously, and after stimulation with anti-CD3, secreted high amounts of interleukin-4 (IL-4) as compared to LNC-purified CD4⁺ and CD8⁺ non-malignant T cells. Furthermore, IL-4 was observed to 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-γ) and was profoundly inhibited by IL-2. Because IL-4 was shown to be a locally active cytokine with a wide range of immunoregulatory properties, regulation of IL-4 production by IFN-γ and IL-2 in malignant T cells may be one of the important parameters to be assessed 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 critical role in PTCL disease mechanism.