Efficacy of pretreatment of allografts with methoxypolyethylene glycol-succinimidyl-propionic acid ester in combination with an anti-OX40L monoclonal antibody in relieving graft-versus-host disease in mice.
We designed to determine whether pretreatment of allografts with methoxypolyethylene glycol-succinimidyl-propionic acid ester (mPEG-SPA) and an anti-OX40L monoclonal antibody (McAb) can relieve acute graft-versus-host disease in allogeneic bone marrow transplantation recipients. Responder splenocytes from C57BL/6 donor mice were incubated with stimulator splenocytes from BALB/c recipient mice for 7 days in the presence or absence of anti-OX40L McAb followed by mPEG-SPA modification. Donor BM cells plus mixed culture T cells were then transplanted into myeloablatively irradiated BALB/c mice. The signs of GVHD were less evident in mice of groups B (mPEG-SPA modification group), C (anti-OX40L McAb pretreated group) and D (dual-treated group), with average survival durations all longer than those in group A (non-treated BMT group) (P < 0.05). The survival rates on day 60 post-BMT in groups B, C and D were 50, 41.7 and 66.7%, respectively. After BMT, serum IL-4 and IL-10 levels elevated in groups B, C (P < 0.05) and even more significantly increased in group D (P < 0.01), while serum IFN-gamma levels decreased in these three groups (P < 0.01). In conclusion, the combination of mPEG-SPA and anti-OX40L McAb can block T cell-activated antigens, co-stimulatory pathways and induce the immune shift of Th cells toward Th2 cells; their effects in ameliorating GVHD are synergistic.
Huang
Yihong
Y
Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China. hxr1583@sina.com
Feng
Saran
S
Tang
Renxian
R
Du
Bing
B
Xu
Kailin
K
Pan
Xiuying
X
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000097:blood; D005260:Female; D006082:Graft Enhancement, Immunologic / Q000379:methods*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053278:OX40 Ligand; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D013154:Spleen / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014184:Transplantation, Homologous; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; C504586:Tnfsf4 protein, mouse; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors; C556225:methoxypolyethylene glycol-succinimidyl-propionic acid ester; D011092:Polyethylene Glycols