Qa-1b and CD94-NKG2a interaction regulate cytolytic activity of herpes simplex virus-specific memory CD8+ T cells in the latently infected trigeminal ganglia

After ocular infection, HSV-specific CD8(+) T cells migrate to and are specifically retained in the ophthalmic branch of the trigeminal ganglia (TG) even at the time when replicating virus is no longer evident. Virus-specific CD8(+) T cells maintain an activation phenotype and secrete IFN-gamma in the latent TG. In this report we demonstrated that activated virus-specific memory CD8(+) T cells, although potentially cytolytic, also expressed the CD94-NK cell receptor subfamily G2a inhibitory molecule and were unable to exert cytotoxicity when engaged by Qa-1(h) expressing targets. Interestingly, many neurons in the latent TG expressed Qa-1(b), and blocking of Qa-1(b)/CD94-NKG2a interaction in an ex vivo TG culture resulted in neuronal cell lysis. The expression of the inhibitory CD94-NKG2a molecule could be induced by TGF-beta 1, which was shown to present as a bioactive molecule in the latent TG. Additionally, CD4(+) forkhead/winged helix transcription factor 3(+) T cells were also determined in the latent TG. Our results demonstrate the operation of a regulatory system in vivo that serves to protect irreplaceable neurons from destruction by the immune system.