Absence of mouse 2B4 promotes NK cell-mediated killing of activated CD8+ T cells, leading to prolonged viral persistence and altered pathogenesis
UMass Chan Affiliations
Department of PathologyDocument Type
Journal ArticlePublication Date
2010-05-05Keywords
AnimalsAntigens, CD3
Killer Cells, Natural
Lymphocytic Choriomeningitis
Lymphocytic choriomeningitis virus
Mice
Mice, Congenic
Mice, Inbred C57BL
Mice, Knockout
NK Cell Lectin-Like Receptor Subfamily D
Perforin
Spleen
T-Lymphocytes
Immunopathology
Life Sciences
Medicine and Health Sciences
Pathology
Metadata
Show full item recordAbstract
Persistent viral infections are often associated with inefficient T cell responses and sustained high-level expression of inhibitory receptors, such as the NK cell receptor 2B4 (also known as CD244), on virus-specific T cells. However, the role of 2B4 in T cell dysfunction is undefined, and it is unknown whether NK cells contribute to regulation of these processes. We show here that persistent lymphocytic choriomeningitis virus (LCMV) infection of mice lacking 2B4 resulted in diminished LCMV-specific CD8+ T cell responses, prolonged viral persistence, and spleen and thymic pathologies that differed from those observed in infected wild-type mice. Surprisingly, these altered phenotypes were not caused by 2B4 deficiency in T cells. Rather, the entire and long-lasting pathology and viral persistence were regulated by 2B4-deficient NK cells acting early in infection. In the absence of 2B4, NK cells lysed activated (defined as CD44hi) but not naive (defined as CD44lo) CD8+ T cells in a perforin-dependent manner in vitro and in vivo. These results illustrate the importance of NK cell self-tolerance to activated CD8+ T cells and demonstrate how an apparent T cell-associated persistent infection can actually be regulated by NK cells.Source
J Clin Invest. 2010 Jun 1;120(6):1925-38. doi: 10.1172/JCI41264. Epub 2010 May 3. Link to article on publisher's siteDOI
10.1172/JCI41264Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39426PubMed ID
20440077; 20440077Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1172/JCI41264