A novel apoptosis-inducing anti-PSGL-1 antibody for T cell-mediated diseases.
We previously discovered a hamster monoclonal antibody, TAB4, against mouse PSGL-1/CD162 that can induce death of activated T cells. Here, we further investigated the potential of TAB4 in treating two murine models of T cell-mediated diseases. The results showed that administration of TAB4 suppressed incidence and severity of both GVHD and type I diabetes. Analyses of apoptotic T cells ex vivo shortly after antibody injection revealed a higher percentage of apoptosis among activated T cells in the TAB4-treated group than in the control group. Furthermore, restoration of functional donor T cells was observed in TAB4-treated mice. As TAB4 does not affect the binding of P-selectin to activated T cells, our data suggest that its long-lasting therapeutic effect on inhibiting disease progression is attained by specifically inducing apoptosis of activated T cells. These data hence extend our previous finding of the novel property of PSGL-1 and strongly indicate that the PSGL-1-specific apoptosis-inducing antibody is a new therapeutic agent possessing a great potential for controlling GVHD and other T cell-mediated autoimmune diseases.
Huang
Chiu-Chen
CC
AbGenomics Co., Neihu, Taipei, Taiwan, ROC.
Lu
Yi-Fen
YF
Wen
Shi-Ni
SN
Hsieh
Wen-Chuan
WC
Lin
Yu-Chin
YC
Liu
Meng-Ru
MR
Chiang
Evelyn
E
Chang
Chung-Nan
CN
Lin
Rong-Hwa
RH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000627:therapeutic use; D017209:Apoptosis / Q000276:immunology*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D019007:P-Selectin / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016207:Cytokines; D008024:Ligands; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein