INVOLVEMENT OF IL-10 IN THE AUTONOMOUS GROWTH OF EBV-TRANSFORMED B-CELL LINES

Immunocompromised individuals have an increased incidence of EBV-assoc iated B cell lymphomas. The growth factors responsible for the unrestr ained proliferation of these lymphomas have not yet been determined. I n this study, spontaneous lymphoblastoid cell lines (SLCL) were derive d without the addition of growth factors or virus from four patients w ith EBV-associated lymphoproliferative disorder. These cell lines were EBV transformed in vivo, and infection was verified through amplifica tion of the viral gp220 gene. SLCL have an activated B cell phenotype (CD19(+), CD21(+), CD23(+), CD38(+), and CD40(+)) and produce IL-6, IL -10, TNF-alpha, and lymphotoxin-alpha. To determine whether these cyto kines contribute to autonomous growth, neutralizing Abs for IL-10, IL- 6, and TNF-alpha, a soluble TNFR:Fc fusion protein, and soluble IL-10R were used. These experiments established that, of the cytokines produ ced by SLCL, only IL-10 is an autocrine factor. IL-10 was produced by the majority of cells within each SLCL, and IL-10 secretion was concom itant with SLCL growth. Our findings demonstrate that IL-10 is utilize d in the autonomous growth of EBV-related lymphomas and may be crucial in the development of lymphoproliferative disorder.