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

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.