Antigen-specific killer polylactic-co-glycolic acid (PLGA) microspheres can prolong alloskin graft survival in a murine model.
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.
Department of Microbiology and Immunology, Medical School, Southeast University , Nanjing, Jiangsu , China .
Wei
W
Wang
Kun
K
Fang
Xiaobing
X
Wang
Miaochen
M
Li
You
Y
Wu
Feng
F
Chen
Khawar Ali
KA
Shahzad
Ning
N
Gu
Chuanlai
C
Shen
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology*; D006183:H-2 Antigens / Q000737:chemistry / Q000276:immunology; D019344:Lactic Acid; D008297:Male; D051379:Mice; D008863:Microspheres; D023421:Models, Animal; D010455:Peptides / Q000276:immunology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016038:Skin Transplantation; D014184:Transplantation, Homologous
D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D010455:Peptides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
Allograft; MHC class I antigen; polylactic-co-glycolic acid (PLGA)