The CD153 vaccine is a senotherapeutic option for preventing the accumulation of senescent T cells in mice.

Yoshida, Shota; Nakagami, Hironori; Hayashi, Hiroki; Ikeda, Yuka; Sun, Jiao; Tenma, Akiko; Tomioka, Hideki; Kawano, Tomohiro et al. · Nat Commun · 2020

basic_science · Level V

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Abstract

Senotherapy targeting for senescent cells is designed to attenuate age-related dysfunction. Senescent T cells, defined as CD4<sup>+</sup> CD44<sup>high</sup> CD62L<sup>low</sup> PD-1<sup>+</sup> CD153<sup>+</sup> 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.

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