cis interaction of CD153 with TCR/CD3 is crucial for the pathogenic activation of senescence-associated T cells

Cell Rep. 2022 Sep 20;40(12):111373. doi: 10.1016/j.celrep.2022.111373.


With age, senescence-associated (SA) CD4+ T cells that are refractory to T cell receptor (TCR) stimulation are increased along with spontaneous germinal center (Spt-GC) development prone to autoantibody production. We demonstrate that CD153 and its receptor CD30 are expressed in SA-T and Spt-GC B cells, respectively, and deficiency of either CD153 or CD30 results in the compromised increase of both cell types. CD153 engagement on SA-T cells upon TCR stimulation causes association of CD153 with the TCR/CD3 complex and restores TCR signaling, whereas CD30 engagement on GC B cells induces their expansion. Administration of an anti-CD153 antibody blocking the interaction with CD30 suppresses the increase in both SA-T and Spt-GC B cells with age and ameliorates lupus in lupus-prone mice. These results suggest that the molecular interaction of CD153 and CD30 plays a central role in the reciprocal activation of SA-T and Spt-GC B cells, leading to immunosenescent phenotypes and autoimmunity.

Keywords: B cells; CD153; CD30; CD4(+) T cells; CP: Immunology; T cell receptor; aging; autoimmune disease; spontaneous germinal center.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / metabolism
  • CD30 Ligand / metabolism*
  • Germinal Center
  • Ki-1 Antigen / metabolism
  • Mice
  • Receptors, Antigen, T-Cell* / metabolism
  • T-Lymphocytes* / metabolism


  • CD3 Complex
  • CD30 Ligand
  • Ki-1 Antigen
  • Receptors, Antigen, T-Cell
  • Tnfsf8 protein, mouse