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In vitro depleting antigen - Specific T cells by a promising toxin antibody conjugate

We further confirm the specificity of toxin-conjugated anti-CD137 mAb showing that only T cells that expressed CD137 underwent apoptosis by staining with toxin-FITC-mAb conjugates. We also found that toxinconjugated anti-CD137 mAb was able to delete allore-active T cells in vitro. Our result indicates that CD137 targeted delivery of toxin is a good strategy to delete antigen-specific T cells. | JOURNAL OF SCIENCE OF HNUE Natural Sci. 2011 Vol. 56 No. 7 pp. 124-131 IN VITRO DEPLETING ANTIGEN - SPECIFIC T CELLS BY A PROMISING TOXIN-ANTIBODY CONJUGATE Chu Dinh Toi Hanoi National University of Education Nguyen Van Diep and Chu Dinh Thien Hanoi University of Agriculture E-mail chudinhtoi@hnue.com.vn Abstract. CD137 expressed on activated T cells is a reliable surrogate marker for antigen specific T cells. In vitro we examined the possibil- ity for toxin-conjugated anti-CD137 mAb to kill CD137-expressing T cells. Doxorubicin and fluorescence were conjugated to anti-CD137 mAb. We observed that fluorescence-conjugated anti-CD137 was internalized into ac- tivated CD4 T cells and CD8 T cells within 4 hours after its treatment and these cell lines constitutively expressed CD137. Doxorubicin-conjugated anti-CD137 mAb induced apoptosis in a majority of CD4 T cells and CD8 T cells within 48 hours after treatment compared with control anti- bodies. We further confirm the specificity of toxin-conjugated anti-CD137 mAb showing that only T cells that expressed CD137 underwent apoptosis by staining with toxin-FITC-mAb conjugates. We also found that toxin- conjugated anti-CD137 mAb was able to delete allore-active T cells in vitro. Our result indicates that CD137 targeted delivery of toxin is a good strategy to delete antigen-specific T cells. Keywords Toxin-antibody conjugate in vitro depleting. 1. Introduction 4-1BB CD137 is an inducible costimulatory molecule expressed on activated T cells CD4 CD8 and NKT 1-4 activated natural killer NK cells dendritic cells DCs eosinophils and mast cells but Myeloid-Derived Suppressor Cells MD- SCs fail to express surface CD137 5 . It is a member of the tumor necrosis factor TNF receptor super family. Its ligand 4-1BBL or CD137L a member of the TNF family is expressed on activated macrophages DCs and B cells etc. Auto-reactive CD4 T-cells with the activated form expresses 4-1BB play important roles in auto-immune diseases by activating