γ-interferon and tumor necrosis factor production after bone marrow transplantation is augmented by exposure to marrow fibroblasts infected with cytomegalovirus

After bone marrow transplantation (BMT), mortality from viral infections such as cytomegalovirus (CMV) remains high. γ-Interferon (γIFN) and tumor necrosis factor (TNF) are produced constitutively after BMT and have anti-viral properties. To study the effects of these cytokines on CMV interaction with host cells, we have used patient marrow fibroblasts since marrow stroma is a target for CMV infection correlating with myelosuppression in vivo. Both γIFN and TNF are constitutively produced by recipient CD3⁺ and CD16⁺ lymphocytes, but not by their marrow fibroblasts. Secretion by peripheral blood mononuclear cells is increased if they are cultured with host fibroblasts infected with CMV in vitro and the levels of γIFN and TNF produced are within the range that protects fresh fibroblasts from CMV infection. Constitutive secretion of cytokines by lymphocytes declines by 8 weeks after BMT, a time when the risk of CMV disease increases sharply. The in vitro phenomenon that we have described needs to be evaluated in correlative studies on individual BMT recipients to determine whether such a cytokine-mediated defense mechanism against CMV may operate in vivo.