Abstract
Senotherapy targeting for senescent cells is designed to attenuate age-related dysfunction. Senescent T cells, defined as CD4+ CD44high CD62Llow PD-1+ CD153+ cells, accumulate in visceral adipose tissues (VAT) in obese individuals. Here, we show 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) conjugate vaccine with Alhydrogel (CD153-Alum) or 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 complement-dependent cytotoxicity (CDC) assay indicated that the mouse IgG2 antibody produced in the CD153-CpG-vaccinated mice successfully reduced the number of senescent T cells. The CD153-CpG vaccine is an optional tool for senolytic therapy.
Highlights
Senotherapy targeting for senescent cells is designed to attenuate age-related dysfunction
We show the long-lasting effect of using CD153 vaccination to prevent the accumulation of adipose senescent T cells from high-fat diet (HFD)-induced obese C57BL/6J mice, accompanied by improved glucose tolerance and insulin resistance
Evaluation of antibody production by the enzymelinked immunosorbent assay (ELISA) showed that the titer against mouse CD153-BSA was initially increased on day 14 in mice immunized with the #A and #C vaccines and successfully increased on day 28 in mice immunized with all five vaccines (Supplementary Fig. 1B)
Summary
Senotherapy targeting for senescent cells is designed to attenuate age-related dysfunction. Senescent T cells (referred to as senescenceassociated T cells; SA-T cells), defined as CD4+ CD44high CD62Llow PD-1+ CD153+ cells, accumulate in visceral adipose tissues (VAT) in obese individuals[11] and produce proinflammatory cytokines, causing chronic inflammation, metabolic disorders, and cardiovascular diseases[12,13]. It is still unknown whether the selective depletion of senescent T cells can attenuate the age-related pathological changes. A complementdependent cytotoxicity (CDC) assay indicates that the mouse IgG2 antibody produced in the CD153-CpG-vaccinated mice successfully reduced the number of senescent T cells
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