Publications by authors named "Alp Oran"

Although endocytosed proteins are commonly presented via the class II MHC pathway to stimulate CD4(+) T cells, professional APCs can also cross-present Ags, whereby these exogenous peptides can be complexed with class I MHC for cross-priming of CD8(+) T cells. Whereas the ability of dendritic cells (DCs) to cross-present Ags is well documented, it is not known whether other APCs may also play a role, or what is the relative contribution of cross-priming to the induction of acquired immunity after DNA immunization. In this study, we compared immune responses generated after gene gun vaccination of mice with DNA vaccine plasmids driven by the conventional CMV promoter, the DC-specific CD11c promoter, or the keratinocyte-specific K14 promoter.

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DNA vaccines represent a novel and powerful alternative to conventional vaccine approaches. They are extremely stable and can be produced en masse at low cost; more importantly, DNA vaccines against emerging pathogens or bioterrorism threats can be quickly constructed based solely upon the pathogen's genetic code. The main drawback of DNA vaccines is that they often induce lower immune responses than traditional vaccines, particularly in nonrodent species.

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For this study, we used DNA-based immunizations to elicit gamma interferon-producing (Tc1) or interleukin 4 (IL-4)-producing (Tc2) CD8 T cells to the influenza virus nucleoprotein. We examined the response of these cells to an intranasal viral challenge. Both the Tc2- and Tc1-biased responses were present in mice with predominantly IL-4-producing (Th2) CD4 T cells.

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Dendritic cells (DCs) are key regulators of immune responses that activate naive antigen-specific T lymphocytes. In draining lymph nodes, antigen-bearing DCs are reported to be rare and short-lived. How such small numbers of short-lived DCs can activate rare antigen-specific T cells is unclear.

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DNA-based immunizations have been used to determine the patterns of type 1 and type 2 cytokines that can be induced in vivo for Ag-specific CD4(+) and CD8(+) T cells. IL-4 was used as a signature cytokine for a type 2 T cell response and IFN-gamma as the signature cytokine for a type 1 response. Gene gun deliveries of secreted Ags were used to bias responses toward type 2 and saline injections of cell-associated Ags to bias responses toward type 1.

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Murine Ag-specific CD8(+) T cells express various NK markers and NK inhibitory receptors that have been proposed to modulate immune responses. Following acute infection of C57BL/6 and BALB/cJ mice with lymphocytic choriomeningitis virus (LCMV), we observed that Ag-specific CD8(+) T cells expressed CD94/NKG2. Only slight expression of Ly49A and Ly49C receptors was observed on NP396-specific T cells, while all NP396-specific T cells expressed the NKT cell marker U5A2-13 Ag.

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