Impact of CD4+ T lymphocytes on the cellular and molecular milieu of the vaginal mucosa following HSV-2 challenge of immune guinea pigs

• Published in: Virology (New York, N.Y.) N.Y.), 2023-11, Vol.588, p.109907, Article 109907
• Main Authors: Bourne, Nigel, Keith, Celeste A., Miller, Aaron L., Pyles, Richard B., Milligan, Gregg N.
• Format: Article
• Language: English
• Subjects: CD4+ T lymphocyte; Chemokine; Cytokine; Guinea pig; HSV-2; Vaginal mucosa; Virus shedding
• ISSN: 0042-6822; 1096-0341; 1096-0341
• DOI: 10.1016/j.virol.2023.109907

CD4+ and CD8+ tissue resident memory cells (TRM) express many shared anti-viral activities upon re-exposure to virus. CD4+ T cells were depleted from HSV-immune guinea pigs to identify CD4-dependent functions in the vaginal mucosa following HSV-2 challenge. The incidence of animals shedding HSV-2 fell rapidly after challenge in control animals but remained significantly higher through day four post infection in CD4-depleted animals. Genes encoding CD14, IFN-γ, CCL2, and CCL5 were up-regulated in the vaginal mucosa of both groups following challenge. However, significantly higher expression of CD107b, IL-15, and TLR9 but lower expression of CD20, IL-21, and CCL5 was detected in CD4-depleted- compared to control-treated animals. Further, antigen stimulation of CD4+ TRM increased the expression of IFN-γ, IL-2, IL-21, IL-17A, and CCL5. The impact of these gene expression patterns on the recruitment and maintenance of the cellular milieu of the vaginal mucosa upon virus challenge is discussed. •CD4-depletion of immune guinea pigs reduces HSV-2 clearance from the vaginal mucosa.•CD4-depletion reduces expression of CD20, IL-21, and CCL5 following HSV-2 challenge.•Vaginal-resident HSV-specific CD4+ T cells express IL-21, IFNγ, and CCL5.•Maintenance of virus specific CD8+ T cells is reduced by CD4-depletion.