Recruitment of bone marrow CD11b+Gr-1+cells by polymeric nanoparticles for antigen cross-presentation.
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-6Chighand CD11b+Gr-1highLy-6Clowsubsets 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.
School of Pharmacy, College of Medicine, National Taiwan University, 33 Linsen South Road, Room 423, Taipei City 10050, Taiwan.
Ya-Wun
YW
Yang
School of Pharmacy, College of Medicine, National Taiwan University, 33 Linsen South Road, Room 423, Taipei City 10050, Taiwan.
Wen-Hui
WH
Luo
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D019070:Cell Lineage; D049109:Cell Proliferation; D018920:Coculture Techniques; D045142:Cross-Priming / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D053804:Granzymes / Q000378:metabolism; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D019344:Lactic Acid / Q000737:chemistry*; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000378:metabolism; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010047:Ovalbumin / Q000276:immunology; D054353:Perforin / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019707:Receptors, Chemokine / Q000378:metabolism*
D015703:Antigens, CD; D015415:Biomarkers; D039481:CD11b Antigen; D016207:Cytokines; C503133:Gr-1 protein, mouse; D007074:Immunoglobulin G; D019707:Receptors, Chemokine; D054353:Perforin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin; D053804:Granzymes