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Journal of Virology, June 2000, p. 5460-5469, Vol. 74, No. 12
Center for Immunization Research, Department
of International Health,1 and Department
of Biology,2 Johns Hopkins University,
Baltimore, Maryland 21205
Received 25 February 2000/Accepted 30 March 2000
During the acute phase of infection with influenza A virus, the
degree of lymphopenia correlates with severity of disease. Factors that
contribute to T-cell activation during influenza virus infection may
contribute to this observation. Since the immune response is initiated
when dendritic cells (DC) interact with T cells, we have established an
in vitro system to examine the effects of influenza virus infection on
DC function. Our results show that allogeneic T-cell proliferation was
dependent on the dose of A/PR/8/34 used to infect DC, with enhanced
responses at low, but not high, multiplicities of infection. The lack
of enhancement at high virus doses was not primarily due to the
increased rate of DC apoptosis, but required viral replication and
neuraminidase (NA) activity. Clusters that formed between DC or between
DC and T cells were also dependent on the viral dose. This change in cellular interaction may oppose T-cell proliferation in response to DC
infected with high doses of PR8, since the increased contact between DC
resulted in the exclusion of T cells. The enhanced alloreactive T-cell
response was restored by neutralization of transforming growth factor
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Dose-Dependent Changes in Influenza Virus-Infected
Dendritic Cells Result in Increased Allogeneic T-Cell Proliferation
at Low, but Not High, Doses of Virus
1 (TGF-
1). It is likely that NA present on viral particles
released from DC infected with high doses of PR8 activates TGF-
1.
Future studies will determine the mechanism by which TGF-
1 modifies
the in vitro T-cell response and address the contribution of this
cytokine to the lymphopenia observed in severe disease.
*
Corresponding author. Mailing address: Department of
International Health, Room 5026, The Johns Hopkins School of Public
Health, 615 N. Wolfe St., Baltimore, MD 21205. Phone: (410) 614-3407. Fax: (410) 955-7159. E-mail: meichelb{at}jhsph.edu.
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