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-1^lowLy-6C^high and CD11b⁺Gr-1^highLy-6C^low 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.