Authors: | Li, R.; Galindo, C. C.; Davidson, D.; Guo, H.; Zhong, M. C.; Qian, J.; Li, B.; Ruzsics, Z.; Lau, C. M.; O'Sullivan, T. E.; Vidal, S. M.; Sun, J. C.; Veillette, A. |
Article Title: | Suppression of adaptive NK cell expansion by macrophage-mediated phagocytosis inhibited by 2B4-CD48 |
Abstract: | Infection of mice by mouse cytomegalovirus (MCMV) triggers activation and expansion of Ly49H+ natural killer (NK) cells, which are virus specific and considered to be “adaptive” or “memory” NK cells. Here, we find that signaling lymphocytic activation molecule family receptors (SFRs), a group of hematopoietic cell-restricted receptors, are essential for the expansion of Ly49H+ NK cells after MCMV infection. This activity is largely mediated by CD48, an SFR broadly expressed on NK cells and displaying augmented expression after MCMV infection. It is also dependent on the CD48 counter-receptor, 2B4, expressed on host macrophages. The 2B4-CD48 axis promotes expansion of Ly49H+ NK cells by repressing their phagocytosis by virus-activated macrophages through inhibition of the pro-phagocytic integrin lymphocyte function-associated antigen-1 (LFA-1) on macrophages. These data identify key roles of macrophages and the 2B4-CD48 pathway in controlling the expansion of adaptive NK cells following MCMV infection. Stimulation of the 2B4-CD48 axis may be helpful in enhancing adaptive NK cell responses for therapeutic purposes. © 2024 The Author(s) |
Keywords: | controlled study; interferon; nonhuman; flow cytometry; cd8+ t lymphocyte; cell proliferation; mouse; animal experiment; animal model; genotype; cell differentiation; cytotoxicity; immune response; hematopoietic cell; natural killer cell; adoptive transfer; cd4 antigen; virus replication; adaptive immunity; macrophage; phagocytosis; cd5 antigen; integrin; cell expansion; t lymphocyte activation; interleukin 12; interleukin 15; fluorescence imaging; lfa-1; programmed death 1 ligand 1; lymphocyte function associated antigen 1; murine cytomegalovirus; macrophage inflammatory protein 1alpha; glycosylphosphatidylinositol; anti-viral immunity; cd48 antigen; slam family receptors; male; female; article; mcmv; 2b4 cell line; cp: immunology; 2b4; adaptive nk cells; bystanding macrophages; cd48; memory nk cells |
Journal Title: | Cell Reports |
Volume: | 43 |
Issue: | 3 |
ISSN: | 2211-1247 |
Publisher: | Cell Press |
Date Published: | 2024-03-26 |
Start Page: | 113800 |
Language: | English |
DOI: | 10.1016/j.celrep.2024.113800 |
PUBMED: | 38386559 |
PROVIDER: | scopus |
DOI/URL: | |
Notes: | Article -- Source: Scopus |