LYMPHOMAGENESIS IN THE SCID-HU MOUSE INVOLVES ABUNDANT PRODUCTION OF HUMAN INTERLEUKIN-10

Both human (hu) and viral (v) interleukin-10 (IL-10) appear to be impo rtant cofactors in the survival and growth of lymphoblastoid cell line s infected with Epstein-Barr virus (EBV). When mice with severe combin ed immune deficiency (SCID) are injected with human peripheral blood l ymphocytes (PBL) from normal individuals who are seropositive for EBV, the majority of hu-PBL-SCID mice will develop an EBV-associated lymph oproliferative disease (EBV-LPD) of human B-cell origin, not unlike so me cases of EBV-LPD that are seen in immunocompromised individuals. Th e role of hulL-10 or vIL-lO in this chimeric mouse model of EBV-LPD is unknown. In the present study, we show that hu-PBL-SCID mice that dev elop EBV-LPD have significant elevation of serum huIL-10 levels compar ed with mice that do not develop EBV-LPD (P = .005). vIL-10 was undete ctable in all animals. The EBV(+) tumor samples express transcript for huIL-10 and huIL-10 receptor, express hulL-10 protein by immunohistoc hemical staining, and show specific binding of recombinant (r) huIL-10 . In vitro analysis of the functional consequences of rhuIL-10 binding to IL-10 receptors on fresh EBV(+) tumor cells shows that rhuIL-10 ca n prevent programmed cell death as well as promote proliferation and c an do so at concentrations of huIL-10 found in vivo. Thus, huIL-10 pro duction by EBV(+) tumor cells may contribute directly to their maligna nt outgrowth in the hu-PBL-SCID mouse by two autocrine mechanisms: pre vention of programmed cell death and proliferation. The implications o f such findings with regard to EBV-LPD in humans is discussed. (C) 199 5 by The American Society of Hematology.