| First Author | Crozat K | Year | 2011 |
| Journal | Blood | Volume | 117 |
| Issue | 10 | Pages | 2874-82 |
| PubMed ID | 21239699 | Mgi Jnum | J:170516 |
| Mgi Id | MGI:4946596 | Doi | 10.1182/blood-2010-10-315457 |
| Citation | Crozat K, et al. (2011) Impact of {beta}2 integrin deficiency on mouse natural killer cell development and function. Blood 117(10):2874-82 |
| abstractText | Natural killer (NK) cells are innate immune cells that express members of the leukocyte beta2 integrin family in humans and mice. These CD11/CD18 heterodimers play critical roles in leukocyte trafficking, immune synapse formation, and costimulation. The cell-surface expression of one of these integrins, CD11b/CD18, is also recognized as a major marker of mouse NK-cell maturation, but its function on NK cells has been largely ignored. Using N-ethyl-N-nitrosourea (ENU) mutagenesis, we generated a mouse carrying an A --> T transverse mutation in the Itgb2 gene, resulting in a mutation that prevented the cell-surface expression of CD18 and its associated CD11a, CD11b, and CD11c proteins. We show that beta2 integrin-deficient NK cells have a hyporesponsive phenotype in vitro, and present an alteration of their in vivo developmental program characterized by a selective accumulation of c-kit(+) cells. NK-cell missing-self recognition was partially altered in vivo, whereas the early immune response to mouse cytomegalovirus (MCMV) infection occurred normally in CD18-deficient mice. Therefore, beta2 integrins are required for optimal NK-cell maturation, but this deficiency is partial and can be bypassed during MCMV infection, highlighting the robustness of antiviral protective responses. |
