AUTHOR=Koelle David M. , Dong Lichun , Jing Lichen , Laing Kerry J. , Zhu Jia , Jin Lei , Selke Stacy , Wald Anna , Varon Dana , Huang Meei-Li , Johnston Christine , Corey Lawrence , Posavad Christine M. 

TITLE=HSV-2-Specific Human Female Reproductive Tract Tissue Resident Memory T Cells Recognize Diverse HSV Antigens

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.867962

DOI=10.3389/fimmu.2022.867962

ISSN=1664-3224

ABSTRACT=<p>Antigen-specific T<sub>RM</sub> 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<sub>RM</sub> persisting at sites of healed human HSV-2 lesions have an activated phenotype but it is unclear if T<sub>RM</sub> can be cultivated <italic>in vitro</italic>. We recovered HSV-specific T<sub>RM</sub> from genital skin and ectocervix biopsies, obtained after recovery from recurrent genital HSV-2, using <italic>ex vivo</italic> activation by viral antigen. Up to several percent of local T cells were HSV-reactive <italic>ex vivo.</italic> CD4 and CD8 T cell lines were up to 50% HSV-2-specific after sorting-based enrichment. CD8 T<sub>RM</sub> 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<sub>RM</sub> 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<sub>RM</sub> 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.</p>