An effector phenotype of CD8+ T cells at the junction epithelium during clinical quiescence of herpes simplex virus 2 infection.
Herpes simplex virus 2 infection is characterized by cycles of viral quiescence and reactivation. CD8(+) T cells persist at the site of viral reactivation, at the genital dermal-epidermal junction contiguous to neuronal endings of sensory neurons, for several months after herpes lesion resolution. To evaluate whether these resident CD8(+) T cells frequently encounter HSV antigen even during times of asymptomatic viral infection, we analyzed the transcriptional output of CD8(+) T cells captured by laser microdissection from human genital skin biopsy specimens during the clinically quiescent period of 8 weeks after lesion resolution. These CD8(+) T cells expressed a characteristic set of genes distinct from those of three separate control cell populations, and network and pathway analyses revealed that these T cells significantly upregulated antiviral genes such as GZMB, PRF1, INFG, IL-32, and LTA, carbohydrate and lipid metabolism-related genes such as GLUT-1, and chemotaxis and recruitment genes such as CCL5 and CCR1, suggesting a possible feedback mechanism for the recruitment of CD8(+) T cells to the site of infection. Many of these transcripts are known to have half-lives of <48 h, suggesting that cognate antigen is released frequently into the mucosa and that resident CD8(+) T cells act as functional effectors in controlling viral spread.
Department of Medicine, University of Washington, Seattle, Washington, USA.
Tao
T
Peng
Jia
J
Zhu
Khamsone
K
Phasouk
David M
DM
Koelle
Anna
A
Wald
Lawrence
L
Corey
D000328:Adult; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002241:Carbohydrates / Q000737:chemistry; D004817:Epidermis / Q000821:virology; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D006561:Herpes Simplex / Q000378:metabolism*; D018258:Herpesvirus 2, Human / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009092:Mucous Membrane / Q000276:immunology / Q000821:virology; D010641:Phenotype; D014158:Transcription, Genetic
D002241:Carbohydrates