Gamma-interferon and tumor necrosis factor production after bone marrow
transplantation is augmented by exposure to marrow fibroblasts infected
with cytomegalovirus
AS Duncombe, A Meager, HG Prentice, JE Grundy, HE Heslop, AV Hoffbrand and MK Brenner
Department of Haematology, Royal Free Hospital, Hampstead, London.
After bone marrow transplantation (BMT), mortality from viral infections
such as cytomegalovirus (CMV) remains high. Gamma-Interferon (gamma IFN)
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 gamma IFN 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 gamma IFN 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.
Volume 76,
Issue 5,
pp. 1046-1053,
09/01/1990
Copyright © 1990 by The American Society of Hematology
