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

Nat Commun. 2020 May 18;11(1):2482. doi: 10.1038/s41467-020-16347-w.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Animals
  • Blood Glucose / metabolism
  • CD30 Ligand / immunology*
  • Cellular Senescence / immunology*
  • Diet, High-Fat
  • Female
  • Glucose Tolerance Test
  • Immunization
  • Insulin Resistance
  • Male
  • Mice, Inbred C57BL
  • Oligodeoxyribonucleotides / immunology
  • Time Factors
  • Vaccines / immunology*

Substances

  • Blood Glucose
  • CD30 Ligand
  • CPG-oligonucleotide
  • Oligodeoxyribonucleotides
  • Vaccines