| First Author | Tripathy SK | Year | 2008 |
| Journal | J Exp Med | Volume | 205 |
| Issue | 8 | Pages | 1829-41 |
| PubMed ID | 18606857 | Mgi Jnum | J:138607 |
| Mgi Id | MGI:3805592 | Doi | 10.1084/jem.20072446 |
| Citation | Tripathy SK, et al. (2008) Continuous engagement of a self-specific activation receptor induces NK cell tolerance. J Exp Med 205(8):1829-41 |
| abstractText | Natural killer (NK) cell tolerance mechanisms are incompletely understood. One possibility is that they possess self-specific activation receptors that result in hyporesponsiveness unless modulated by self-major histocompatability complex (MHC)-specific inhibitory receptors. As putative self-specific activation receptors have not been well characterized, we studied a transgenic C57BL/6 mouse that ubiquitously expresses m157 (m157-Tg), which is the murine cytomegalovirus (MCMV)-encoded ligand for the Ly49H NK cell activation receptor. The transgenic mice were more susceptible to MCMV infection and were unable to reject m157-Tg bone marrow, suggesting defects in Ly49H(+) NK cells. There was a reversible hyporesponsiveness of Ly49H(+) NK cells that extended to Ly49H-independent stimuli. Continuous Ly49H-m157 interaction was necessary for the functional defects. Interestingly, functional defects occurred when mature wild-type NK cells were adoptively transferred to m157-Tg mice, suggesting that mature NK cells may acquire hyporesponsiveness. Importantly, NK cell tolerance caused by Ly49H-m157 interaction was similar in NK cells regardless of expression of Ly49C, an inhibitory receptor specific for a self-MHC allele in C57BL/6 mice. Thus, engagement of self-specific activation receptors in vivo induces an NK cell tolerance effect that is not affected by self-MHC-specific inhibitory receptors. |
