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-1b expressing targets. Interestingly, many neurons in the latent TG expressed Qa-1b, and blocking of Qa-1b/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-beta1, 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.
Suvas
Susmit
S
Department of Microbiology, University of Tennessee, Knoxville, TN 37996, USA. ssuvas@utk.edu
Azkur
Ahmet Kursat
AK
Rouse
Barry T
BT
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D055607:Receptors, Natural Killer Cell; D018139:Simplexvirus / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D017735:Virus Latency / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015395:Histocompatibility Antigens Class I; C527057:Klrc1 protein, mouse; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; C032907:Q surface antigens; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell