Abstract
The objective of this study was to investigate the function of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on the activation of antigen-specific CD8+ T cell responses via the CD11b+Gr−1+ myeloid subpopulations in murine bone marrow (BM). PLGA NPs containing ovalbumin (OVA) were fabricated by the double-emulsion method. The CD11b+Gr-1lowLy-6Chigh and CD11b+Gr-1highLy-6Clow subsets from mice bone marrow were sorted and treated with the PLGA/OVA NPs, followed by co-culture with the carboxyfluorescein succinimidyl ester (CFSE)-labelled OT-I CD8+ cells. Co-culture of OT-I CD8+ T cells with PLGA/OVA NPs-primed CD11b+Gr-1+ subsets upregulated the expression of IL-2, TNF-α, INF-γ, granzyme B, and perforin, resulting in proliferation of CD8+ T cells and differentiation into effector cytotoxic T lymphocytes (CTLs). In vivo proliferation of CFSE-labelled OT-I CD8+ cells in response to OVA was also obtained in the animals immunized with PLGA/OVA NPs. The results presented in this study demonstrate the ability of polymeric NPs to recruit two CD11b+Gr−1+ myeloid subsets for effective presentation of exogenous antigen to OT-I CD8+ T cells in the context of major histocompatibility complex (MHC) class I, leading to an induction of antigen-specific cell proliferation and differentiation into effector cells.
Highlights
The objective of this study was to investigate the function of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on the activation of antigen-specific CD8+ T cell responses via the CD11b+Gr−1+
We investigated the potential recruitment of polymorphonuclear (PMN) granulocytes from the mouse bone marrow (BM) by polymeric nanoparticles (NPs) for cross-presentation of exogenous antigens and stimulation of cytotoxic T lymphocyte (CTL) effector functions
In view of the emergence of nanotechnology and the potential application of polymeric nanoparticles in cancer vaccines, we investigated in this study the combined potential of polymeric nanoparticles and the phagocytic capability of bone marrow Gr-1+ granulocytes, including the Gr-1high and Gr-1low subsets, for cross presentation of exogenous antigens to boost the major histocompatibility complex (MHC) class I immune response
Summary
The objective of this study was to investigate the function of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on the activation of antigen-specific CD8+ T cell responses via the CD11b+Gr−1+. In vivo proliferation of CFSE-labelled OT-I CD8+ cells in response to OVA was obtained in the animals immunized with PLGA/OVA NPs. The results presented in this study demonstrate the ability of polymeric NPs to recruit two CD11b+Gr−1+ myeloid subsets for effective presentation of exogenous antigen to OT-I CD8+ T cells in the context of major histocompatibility complex (MHC) class I, leading to an induction of antigen-specific cell proliferation and differentiation into effector cells. Our recent study demonstrated the activation of CD8+ T cells by the nanoparticles-primed Gr-1high cells[18] These results prompted us to further evaluate the potential of granulocytes from murine bone marrow to induce activation of cytotoxic T lymphocyte (CTL) effectors in nanoparticle (NPs)-based vaccination. Correspondence and requests for materials should be addressed to Y.-W.Y. (email: ywyang@ntu. edu.tw) www.nature.com/scientificreports/
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