Research ArticleT CELLS

Persistent antigen exposure via the eryptotic pathway drives terminal T cell dysfunction

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Science Immunology  26 Feb 2021:
Vol. 6, Issue 56, eabe1801
DOI: 10.1126/sciimmunol.abe1801

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Co-opting erythrocyte clearance

While T cell dysfunction contributes to immune evasion in cancer and chronic viral infection, strategies that induce dysfunction in autoreactive T cells may facilitate self-tolerance. Watkins et al. used phage display to identify a human antibody fragment (Fab) that selectively binds erythrocytes, enabling efficient antigen targeting to splenic antigen-presenting cells that rapidly clear apoptotic erythrocytes. Fab-tethered antigen induced antigen-specific T cell dysfunction in mice that was sustained in response to antigen rechallenge for at least 3 months and required Batf3-dependent dendritic cells. In a murine model of experimental autoimmune encephalomyelitis, erythrocyte-targeted antigen prevented encephalogenic T cells from contributing to autoimmune pathology, demonstrating the therapeutic potential of leveraging erythrocyte clearance pathways to disarm overactive T cells.

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