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Human cytomegalovirus-associated immunosuppression is mediated through
interferon-alpha
N Noraz, JL Lathey and SA Spector
Department of Pediatrics, University of California, San Diego, La Jolla
92093-0672, USA.
Human cytomegalovirus (HCMV) infections are commonly associated with a
generalized immunologic hyporesponsiveness. The present study was designed
to evaluate the potential mechanisms of HCMV-associated immunosuppression.
In our initial experiments, monocytes in peripheral blood mononuclear cells
(PBMCs) exposed to cell-free HCMV appeared morphologically less
differentiated than monocytes in PBMCs exposed to a mock preparation. These
morphologic changes were closely correlated with a decrease in monocyte
oxidative activity and occurred under noncytopathic conditions.
HCMV-associated suppression of monocyte differentiation did not require
virus replication, occurred in PBMCs from either HCMV seropositive or
seronegative donors, and required HCMV interaction with the nonadherent
cells. An HCMV-induced soluble factor was found to not only reproduce the
identical changes in purified monocytes but to inhibit the phagocytic
activity of these cells. Additionally, the HCMV-induced factor accounted
for a generalized defect in the ability of PBMCs to proliferate in response
to mitogens and recall antigens. In subsequent experiments,
interferon-alpha (IFN- alpha) was identified as the soluble factor involved
in these immunosuppressive effects. Thus, PBMCs, when exposed to HCMV,
produce a soluble factor, identified as IFN-alpha, that appears to be an
important mediator of immunosuppression associated with HCMV infection.
Volume 89,
Issue 7,
pp. 2443-2452,
04/01/1997
Copyright © 1997 by The American Society of Hematology
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