CEACAM1 promotes CD8(+) T cell responses and improves control of a chronic viral infection

Khairnar, Vishal; Duhan, Vikas; Patil, Ashwini M.; Zhou, Fan; Bhat, Hilal; Thoens, Christine; Sharma, Piyush; Adomati, Tom; Friendrich, Sarah-Kim; Bezgovsek, Judith; Dreesen, Janine D.; Wennemuth, Gunther; Westendorf, Astrid M.; Zelinskyy, Gennadiy; Dittmer, Ulf; Hardt, Cornelia; Timm, Jörg; Göthert, Joachim R.; Lang, Philipp A.; Singer, Bernhard B.; Lang, Karl S.

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.