Journal Article

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

Morishita, Ryuichi, Rakugi, Hiromi, Tenma, Akiko, Yoshida, Shota, Hayashi, Hiroki, Shimamura, Munehisa, Tomioka, Hideki, Ikeda, Yuka, Nakagami, Hironori, Kawano, Tomohiro, Sun, Jiao

2020

Overview

Senotherapy targeting for senescent cells is designed to attenuate age-related dysfunction. Senescent T cells, defined as CD4 + CD44 high CD62L low 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. Senotherapy, the removal of aged T cells, is an effective approach to attenuate age-related diseases. Here the authors report a CD153 targeting vaccine that prevents the accumulation of senescent adipose tissue T cells in mice on high-fat diet, which is associated with improved glucose tolerance.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 13/31 / 38 / 631/250/590/2030 / 631/443/319/1642/393 / 82/1 / 82/29 / 82/51 / 96/63 / Accumulation / Adipose tissue / Adipose Tissue - cytology / Age / Age related diseases / Animals / Antibodies / Blood Glucose - metabolism / CD30 Ligand - immunology / CD4 antigen / Cellular Senescence - immunology / CpG islands / Cytotoxicity / Diet / Diet, High-Fat / Female / Glucose / Glucose tolerance / Glucose Tolerance Test / High fat diet / Humanities and Social Sciences / Immunization / Immunoglobulin G / Immunological tolerance / Insulin / Insulin Resistance / Lymphocytes / Lymphocytes T / Male / Mice, Inbred C57BL / multidisciplinary / Oligodeoxyribonucleotides - immunology / Oligonucleotides / PD-1 protein / Science / Science (multidisciplinary) / Time Factors / Toxicity / Vaccination / Vaccines / Vaccines - immunology