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

Fukushima, Yuji Sakamoto, Keiko Matsuda, Michiyuki Yoshikai, Yasunobu Yagita, Hideo Kitamura, Daisuke Chihara, Misaki Minato, Nagahiro Hattori, Masakazu 京都大学 DOI:10.1016/j.celrep.2022.111373

2022.09.20

概要

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.

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