CXCL10 chemokine regulates heterogeneity of the CD8+ T cell response and viral set point during chronic infection
| Autor: | Thorsten R. Mempel, Philippe Dehio, Andrew D. Luster, Aleksandra J. Ozga, Rachel L. Servis, Mateus E. Lopes, Mauro Di Pilato, Jeffrey Lian, Melvyn T. Chow |
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| Rok vydání: | 2022 |
| Předmět: |
White pulp
Chemokine Receptors CXCR3 Immunology CD8-Positive T-Lymphocytes Lymphocytic Choriomeningitis Biology Lymphocytic choriomeningitis CXCR3 Article B7-H1 Antigen Monocytes Mice medicine Animals Lymphocytic choriomeningitis virus Immunology and Allergy Cytotoxic T cell CXCL10 Hepatocyte Nuclear Factor 1-alpha Cell Self Renewal Clonal Selection Antigen-Mediated Cell Proliferation Mice Knockout Cell Differentiation medicine.disease Chemokine CXCL10 Mice Inbred C57BL Chronic infection Infectious Diseases medicine.anatomical_structure Chronic Disease biology.protein Female Spleen CD8 |
| Zdroj: | Immunity |
| ISSN: | 1074-7613 |
| Popis: | CD8(+) T cells responding to chronic infection adapt an altered differentiation program that provides some restrain on pathogen replication yet limits immunopathology. This adaptation is imprinted in stem-like cells and propagated to their progeny. Understanding the molecular control of CD8(+) T cell differentiation in chronic infection has important therapeutic implications. Here, we found that the chemokine receptor CXCR3 was highly expressed on viral-specific stem-like CD8(+) T cells and that one of its ligands, CXCL10, regulated the persistence and heterogeneity of responding CD8(+) T cells in spleens of mice chronically infected with lymphocytic choriomeningitis virus. CXCL10 was produced by inflammatory monocytes and fibroblasts of the splenic red pulp where it granted stem-like cells access to signals promoting differentiation and limited their exposure to pro-survival niches in the white pulp. Consequently, functional CD8(+) T cell responses were greater in Cxcl10(−/−) mice and were associated with a lower viral set point. |
| Databáze: | OpenAIRE |
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