Investigating the Distinct Tissue Repair and Immunosuppressive Roles of Regulatory T cells in HSV-2 Infection

Abstract Herpes Simplex Virus 2 (HSV-2) is the primary cause of genital herpes, affecting 500 million people worldwide which approximately 64% are women. Despite this disproportionately high burden, female reproductive tract and its unique mucosal immune environment surprisingly understudied. Tregs necessary for CD4 +T cell priming in draining lymph node (dLN), though their role shaping tissue-resident memory T (T rm) responses during HSV-2 reactivation unclear. Our preliminary data indicate that activated accumulate persist mouse vaginal tissue (VT) after above baseline out to at least 90 days post-infection (p.i.), thus implicating recall reinfection. We hypothesize restrain robust rmrecall challenge. Additionally, we promote healing VT response inflammatory alarmins through expression epidermal growth factor ligand, amphiregulin (Areg). Female FoxP3 DTRmice were infected intravaginally with attenuated HSV-2, then systemically depleted via intraperitoneal injection diphtheria toxin challenged WT on day 30 p.i. Systemically Treg-depleted mice show increased activation proliferation cells, frequency cytotoxic HSV-2-specific CD8 cells by 3 post-challenge. also have significantly higher pathology scores H&E-stained VT. report from express more Areg than dLN flow cytometry single RNAseq. Ongoing work includes characterization expressing further dissection mice. NIH (T32 AI07140, R01 AI141435)