Unknown

Dataset Information

0

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


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.

SUBMITTER: Khairnar V 

PROVIDER: S-EPMC6028648 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications


Dysfunction of CD8<sup>+</sup> 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 f  ...[more]

Similar Datasets

| S-EPMC6996002 | biostudies-literature
| S-EPMC4349659 | biostudies-literature
| S-EPMC3141034 | biostudies-literature
| S-EPMC4323683 | biostudies-literature
| S-EPMC7212788 | biostudies-literature
| S-EPMC2774709 | biostudies-literature
| S-EPMC3572910 | biostudies-literature
| S-EPMC5753758 | biostudies-literature
| S-EPMC4427042 | biostudies-literature
| S-EPMC5398720 | biostudies-literature