Continuous engagement of a self-specific activation receptor induces NK cell tolerance

Sandeep K Tripathy, Peter Keyel, Liping Yang, Jeanette T Pingel, Tammy P Cheng, A Schneeberger, Wayne M Yokoyama

Research output: Contribution to journalArticle

Abstract

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 th
Original languageEnglish
Pages (from-to)1829-1841
JournalJournal of Experimental Medicine
StatePublished - 2008

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