Interleukin-18, interferon-gamma, IP-10, and Mig expression in Epstein-Barr virus-induced infectious mononucleosis and posttransplant lymphoproliferative disease

T cell immunodeficiency plays an important role in the pathogenesis of post transplant lymphoproliferative disease (PTLD) by permitting the unbridled e xpansion of Epstein-Barr virus (EBV)-infected B lymphocytes. However, facto rs other than T cell function may contribute to PTLD pathogenesis because P TLD infrequently develops even in the context of severe T cell immunodefici ency, and athymic mice that are T-cell-immunodeficient can reject EBV-immor talized cells. Here we report that PTLD tissues express significantly lower levels of IL-18, interferon-gamma (IFN-gamma), Mig, and RANTES compared to lymphoid tissues diagnosed with acute EBV-induced infectious mononucleosis , as assessed by semiquantitative RT-PCR analysis. Other cytokines and chem okines are expressed at similar levels. Immunohistochemistry confirmed that PTLD tissues contain less IL-18 and Mig protein than tissues with infectio us mononucleosis. IL-18, primarily a monocyte product, promotes the secreti on of IFN-gamma, which stimulates Mig and RANTES expression. Both IL-18 and Mig display antitumor activity in mice involving inhibition of angiogenesi s, These results document greater expression of IL-18, IFN-gamma, Mig, and RANTES in lymphoid tissues with acute EBV-induced infectious mononucleosis compared to tissues with PTLD and raise the possibility that these mediator s participate in critical host responses to EBV infection.