Abstract:
:Dysfunction of CD8+ T cells can lead to the development of chronic viral infection. Identifying mechanisms responsible for such T cell dysfunction is therefore of great importance to understand how to prevent persistent viral infection. Here we show using lymphocytic choriomeningitis virus (LCMV) infection that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is fundamental for recruiting lymphocyte-specific protein kinase (Lck) into the T cell receptor complex to form an efficient immunological synapse. CEACAM1 is essential for activation of CD8+ T cells, and the absence of CEACAM1 on virus-specific CD8+ T cells limits the antiviral CD8+ T cell response. Treatment with anti-CEACAM1 antibody stabilizes Lck in the immunological synapse, prevents CD8+ T cell exhaustion, and improves control of virus infection in vivo. Treatment of human virus-specific CD8+ T cells with anti-CEACAM1 antibody similarly enhances their proliferation. We conclude that CEACAM1 is an important regulator of virus-specific CD8+ T cell functions in mice and humans and represents a promising therapeutic target for modulating CD8+ T cells.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Khairnar V,Duhan V,Patil AM,Zhou F,Bhat H,Thoens C,Sharma P,Adomati T,Friendrich SK,Bezgovsek J,Dreesen JD,Wennemuth G,Westendorf AM,Zelinskyy G,Dittmer U,Hardt C,Timm J,Göthert JR,Lang PA,Singer BB,Lang KSdoi
10.1038/s41467-018-04832-2subject
Has Abstractpub_date
2018-07-02 00:00:00pages
2561issue
1issn
2041-1723pii
10.1038/s41467-018-04832-2journal_volume
9pub_type
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