A novel apoptosis-inducing anti-PSGL-1 antibody for T cell-mediated diseases

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Abstract
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.

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