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-treated human dendritic cells for efficient initiation of specific type 1 immune responses in vitro




* Laboratory of Immunology, Istituto Dermopatico dellImmacolata, IRCCS, Rome, Italy; and
Institute of Biochemistry Giorgio Fornaini, University of Urbino, Italy
Correspondence: Dr. Silvia Corinti, Laboratory of Immunology, Istituto Dermopatico dellImmacolata, IRCCS, Via Monti di Creta 104, 00167 Roma, Italy. E-mail: s.corinti{at}idi.it
Dendritic cells (DC) can represent an important target for vaccine development against viral infections. Here, we studied whether interferon-
(IFN-
) could improve the functions of DC and analyzed human red blood cells (RBC) as a delivery system for Tat protein. Monocyte-derived DC were cultured in human serum and matured with monocyte-conditioned medium (MCM) in the presence or not of IFN-
. Tat was conjugated to RBC (RBC-Tat) through avidin-biotin bridges. Stimulation of DC with IFN-
increased the release of interleukin (IL)-12 and tumor necrosis factor-
and inhibited the production of IL-10. Moreover, IFN-
-treated DC up-regulated the release of CXCL10 (IP-10) markedly and reduced the secretion of CCL17 TARC significantly, attracting preferentially T-helper (Th)1 and Th2 cells, respectively. DC internalized RBC-Tat efficiently. Compared with DC pulsed with soluble Tat, DC incubated with RBC-Tat elicited specific CD4+ and CD8+ T-cell responses at a much lower antigen dose. DC matured in the presence of MCM were more effective than immature DC in inducing T-cell proliferation and IFN-
release. Finally, immature and mature DC exposed to IFN-
were better stimulators of allogeneic T cells and induced a higher IFN-
production from Tat-specific CD4+ and CD8+ T lymphocytes. In conclusion, erythrocytes appear an effective tool for antigen delivery into DC, and IFN-
could be used advantageously for augmenting the ability of DC to induce type 1 immune responses.
Key Words: T lymphocytes AIDS cytokines chemokines vaccination
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