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

Nat Commun. 2018 Jul 2;9(1):2561. doi: 10.1038/s41467-018-04832-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, CD / metabolism*
  • Bone Marrow Transplantation
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / metabolism*
  • Cell Adhesion Molecules / metabolism*
  • Chimera
  • Chronic Disease
  • Female
  • Humans
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic Choriomeningitis / virology
  • Lymphocytic choriomeningitis virus / immunology*
  • Lymphocytic choriomeningitis virus / pathogenicity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic

Substances

  • Antigens, CD
  • CD66 antigens
  • Carcinoembryonic Antigen
  • Ceacam1 protein, mouse
  • Cell Adhesion Molecules
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)