T-CELL DERIVED CYTOKINES CO-STIMULATE PROLIFERATION OF CD40-ACTIVATEDGERMINAL CENTER AS WELL AS FOLLICULAR LYMPHOMA-CELLS

Follicular lymphomas, the malignant counterparts of normal germinal ce ntre (GC) B-cells, grow in vivo in close association with polyclonal T -cells, predominantly from the T-helper cell type. T-cell-derived grow th factors are involved in the development of GC B-cells. However, the ir role in the pathogenesis of follicular lymphomas has not been clear ly defined. We investigated the co-stimulatory activity of 14 cytokine s (interleukin-l to -8, IL-10, IL-13, IFN-a, TNF-a, GM-CSF and SCF) on the proliferation of CD40-activated follicular lymphoma cells in comp arison to tonsillar GC B-cells. Tonsillar GC B-cells (n=4), malignant cells from diagnostic lymph node biopsies of patients with follicular (n=4) or transformed (n=4) lymphomas were grown on irradiated CD40-lig and transfectants, with and without cytokines. [H-3]-thymidine uptake was measured at day 7. IL-10 and IL-4 proved to be the most potent co- stimulators of proliferation of tonsillar GC B-cells, whereas prolifer ation of follicular lymphoma cells was co-stimulated by IL-4. The fact that IL-4 is a T-cell derived cytokine, suggests that lymphoma infilt rating T-cells play a role in the growth of these malignancies. Moreov er, proliferation of both non-neoplastic tonsillar GC B-cells and foll icular lymphomas is co-stimulated by T-cell derived cytokines, indicat ing that responsiveness to paracrine factors may not be a characterist ic of the malignant phenotype. (C) 1997 John Wiley & Sons, Ltd.