PubMed ID

20440077

UMMS Affiliation

Department of Pathology

Date

5-5-2010

Document Type

Article

Subjects

Animals; Antigens, 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

Disciplines

Immunopathology | Life Sciences | Medicine and Health Sciences | Pathology

Abstract

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.

Rights and Permissions

Citation: J Clin Invest. 2010 Jun 1;120(6):1925-38. doi: 10.1172/JCI41264. Epub 2010 May 3. Link to article on publisher's site

Related Resources

Link to Article in PubMed