CEACAM1 promotes CD8+ T cell responses and improves control of a chronic viral infection
| Autor: | Gennadiy Zelinskyy, Jörg Timm, Tom Adomati, Cornelia Hardt, Judith Bezgovsek, Joachim R. Göthert, Ashwini M Patil, Vishal Khairnar, Bernhard B. Singer, Karl S. Lang, Astrid M. Westendorf, Vikas Duhan, Philipp A. Lang, Sarah-Kim Friendrich, Janine D. Dreesen, Hilal Bhat, Gunther Wennemuth, Piyush Sharma, Ulf Dittmer, Fan Zhou, Christine Thoens |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Adoptive cell transfer T cell receptor complex T cell viruses Science Medizin General Physics and Astronomy Mice Transgenic CD8-Positive T-Lymphocytes Lymphocytic Choriomeningitis General Biochemistry Genetics and Molecular Biology Article Immunological synapse 03 medical and health sciences Mice Antigen Antigens CD medicine Cytotoxic T cell Animals Humans Lymphocytic choriomeningitis virus lcsh:Science Bone Marrow Transplantation Multidisciplinary Chemistry Cell adhesion molecule Chimera General Chemistry Adoptive Transfer Cell biology Carcinoembryonic Antigen Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Chronic Disease lcsh:Q Female Cell Adhesion Molecules CD8 |
| Zdroj: | Nature Communications Nature Communications, Vol 9, Iss 1, Pp 1-14 (2018) |
| ISSN: | 2041-1723 |
| Popis: | 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. Chronic viral infections are frequently associated with the dysfunction of CD8+ T cells which includes loss of function and results in CD8+ T cell exhaustion. Here the authors show a role of CEACAM1 in promoting responsive CD8+ T cells in the context of a chronic lymphocytic choriomeningitis virus (LCMV) infection model. |
| Databáze: | OpenAIRE |
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