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* Department of Medicine, Center for Infectious Medicine, Huddinge University Hospital, and
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden;
Swedish Institute for Infectious Disease Control, Stockholm, Sweden;
Cancer Center, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden; and
¶ Department of Health and Society, Malmö University, Malmö, Sweden
Ag-presenting dendritic cells present viral Ags to T cells after
uptake of apoptotic bodies derived from virus-infected cells in vitro.
However, it is unclear whether apoptotic virus-infected cells are
capable of generating immunity in vivo. In this study, we show that
inoculation of mice with apoptotic HIV-1/murine leukemia virus
(MuLV)-infected cells induces HIV-1-specific immunity. Immunization
with apoptotic HIV-1/MuLV-infected syngeneic splenocytes resulted in
strong Nef-specific CD8+ T cell proliferation and
p24-induced CD4+ and CD8+ T cell proliferation
as well as IFN-
production. In addition, systemic IgG and IgA as
well as mucosa-associated IgA responses were generated. Moreover, mice
vaccinated with apoptotic HIV-1/MuLV cells were protected against
challenge with live HIV-1/MuLV-infected cells, whereas mice vaccinated
with apoptotic noninfected or MuLV-infected splenocytes remained
susceptible to HIV-1/MuLV. These data show that i.p. immunization with
apoptotic HIV-1-infected cells induces high levels of HIV-1-specific
systemic immunity, primes for mucosal immunity, and induces protection
against challenge with live HIV-1-infected cells in mice. These
findings may have implications for the development of therapeutic and
prophylactic HIV-1 vaccines.
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