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

Yuji Fukushima, Keiko Sakamoto, Michiyuki Matsuda, Yasunobu Yoshikai, Hideo Yagita, Daisuke Kitamura, Misaki Chihara, Nagahiro Minato, Masakazu Hattori

Cell reports 2022 Sep 20

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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. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Yuji Fukushima, Keiko Sakamoto, Michiyuki Matsuda, Yasunobu Yoshikai, Hideo Yagita, Daisuke Kitamura, Misaki Chihara, Nagahiro Minato, Masakazu Hattori. cis interaction of CD153 with TCR/CD3 is crucial for the pathogenic activation of senescence-associated T cells. Cell reports. 2022 Sep 20;40(12):111373