Antigen-specific T persist and protect against skin or female reproductive tract (FRT) HSV infection. As the pathogenesis of HSV differs between humans and model organisms, we focus on humans with well-characterized recurrent genital HSV-2 infection. Human CD8+ T persisting at sites of healed human HSV-2 lesions have an activated phenotype but it is unclear if T can be cultivated . We recovered HSV-specific T from genital skin and ectocervix biopsies, obtained after recovery from recurrent genital HSV-2, using activation by viral antigen. Up to several percent of local T cells were HSV-reactive CD4 and CD8 T cell lines were up to 50% HSV-2-specific after sorting-based enrichment. CD8 T displayed HLA-restricte... More
Antigen-specific T persist and protect against skin or female reproductive tract (FRT) HSV infection. As the pathogenesis of HSV differs between humans and model organisms, we focus on humans with well-characterized recurrent genital HSV-2 infection. Human CD8+ T persisting at sites of healed human HSV-2 lesions have an activated phenotype but it is unclear if T can be cultivated . We recovered HSV-specific T from genital skin and ectocervix biopsies, obtained after recovery from recurrent genital HSV-2, using activation by viral antigen. Up to several percent of local T cells were HSV-reactive CD4 and CD8 T cell lines were up to 50% HSV-2-specific after sorting-based enrichment. CD8 T displayed HLA-restricted reactivity to specific HSV-2 peptides with high functional avidities. Reactivity to defined peptides persisted locally over several month and was quite subject-specific. CD4 T derived from biopsies, and from an extended set of cervical cytobrush specimens, also recognized diverse HSV-2 antigens and peptides. Overall we found that HSV-2-specific T are abundant in the FRT between episodes of recurrent genital herpes and maintain competency for expansion. Mucosal sites are accessible for clinical monitoring during immune interventions such as therapeutic vaccination.
