PS-B03-3: THE CD153-CPG VACCINE IS A NOVEL SENOTHERAPEUTIC OPTION TO REMOVE SENESCENCE-ASSOCIATED T CELLS

Abstract

Cellular senescence in primary culture cells has allowed us to understand basic individual tissue aging and cancer inhibition from the view of cellular aging. Senescent cells accumulate gradually and systemically with age, and secrete various inflammatory cytokines or chemokines, which is different from the cell fate in apoptosis. These phenomena describe the so-called senescence-associated secretory phenotype, and chronic inflammation and carcinogenesis are induced in the surrounding tissues through senescence-associated secretory phenotype factors. The senescence-associated T cells do not proliferate in response to T-cell receptor stimulation, and produce abundant inflammatory cytokines including osteopontin. Senescence-associated T cells are also increased in adipose tissue under a high-fat diet, which might be related to the progress of obesity or diabetes. We evaluated the long-lasting effect of using CD153 vaccination to remove senescent T cells from high-fat diet (HFD)-induced obese C57BL/6J mice. We administered a CD153 peptide-KLH (keyhole limpet hemocyanin) vaccine with CpG oligodeoxynucleotide (ODN) 1585 (CD153-CpG) and confirmed an increase in anti-CD153 antibody levels that was sustained for several months. After being fed a HFD for 10–11 weeks, adipose senescent T cell accumulation was significantly reduced in the VAT of CD153-CpG-vaccinated mice, accompanied by glucose tolerance and insulin resistance. A histological analysis also indicated that the accumulation of macrophages and senescence-associated T cells in adipose tissues successfully reduced in the CD153-CpG-vaccinated mice. The CD153-CpG vaccine is an optional tool for senolytic therapy. We further modify the vaccine to remove the target cells now.