Antigen-Specific Killer Polylactic-Co-Glycolic Acid (PLGA) Microspheres Can Prolong Alloskin Graft Survival in a Murine Model

Abstract

Background: The strategy of specifically depleting antigen-specific T cells can potentially be used for the treatment of allograft rejection and autoimmunity because it does not suppress the overall immune systems.

Methods: In this study, we generated killer polylactic-co-glycolic acid (PLGA) microspheres by covalently coupling major histocompatibility complex (MHC) class I antigens and apoptosis-inducing anti-Fas monoclonal antibody (mAb) onto PLGA microspheres. A modified double-emulsion method was used for the preparation of cell-sized PLGA microspheres. H-2K^b/peptide monomers were generated in-house and analyzed through flow cytometry. The killer PLGA microspheres were administered intravenously into BALB/c mice (H-2K^d) that had previously been grafted with skin squares from C57BL/6 mice (H-2K^b). Tumor cell challenge and third-party mixed lymphocyte culture were used to assess the general immune functions of host.

Results: The alloskin graft survival was prolonged by 4 days. The killer PLGA microspheres could specifically deplete the H-2K^b alloantigen-reactive CD8⁺ T cells that infiltrated into the alloskin graft but not CD4⁺ T cells, without impairment of host overall immune function.

Conclusions: Here, we initially report that PLGA microspheres, which have been widely used as medicine-delivering carriers, were used to prepare antigen-specific killer complexes and treat allograft rejection. Our data highlight the therapeutic potential of this biocompatible and biodegradable antigen-specific killer effector for the treatment of allograft rejection and autoimmune disease.

• Allograft
• MHC class I antigen
• polylactic-co-glycolic acid (PLGA)

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

This work was supported by the National Nature Science Foundation of China (81172823 and 81372448) to C.S.