High Frequencies of Antiviral Effector Memory TEM Cells and Memory B Cells Mobilized into Herpes Infected Vaginal Mucosa Associated With Protection Against Genital Herpes

Nisha Rajeswari Dhanushkodi; Swayam Prakash; Afshana Quadiri; Latifa Zayou; Mahmoud Singer; Nakayama Takashi; Hawa Vahed; Lbachir BenMohamed

doi:10.1101/2023.05.23.542021

High Frequencies of Antiviral Effector Memory T_EM Cells and Memory B Cells Mobilized into Herpes Infected Vaginal Mucosa Associated With Protection Against Genital Herpes

bioRxiv [Preprint]. 2023 May 24:2023.05.23.542021. doi: 10.1101/2023.05.23.542021.

Authors

Affiliations

¹ Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697.
² Kindai University, Higashiosaka, Osaka 577-8502, Japan.
³ Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA 92660; USA.
⁴ Department of Molecular Biology and Biochemistry; the University of California Irvine, School of Medicine, Irvine, CA 92697.
⁵ Institute for Immunology; the University of California Irvine, School of Medicine, Irvine, CA 92697.

Abstract

Vaginal mucosa-resident anti-viral effector memory B- and T cells appeared to play a crucial role in protection against genital herpes. However, how to mobilize such protective immune cells into the vaginal tissue close to infected epithelial cells remains to be determined. In the present study, we investigate whether and how, CCL28, a major mucosal-associated chemokine, mobilizes effector memory B- and T cells in leading to protecting mucosal surfaces from herpes infection and disease. The CCL28 is a chemoattractant for the CCR10 receptor-expressing immune cells and is produced homeostatically in the human vaginal mucosa (VM). We found the presence of significant frequencies of HSV-specific memory CCR10⁺CD44⁺CD8⁺ T cells, expressing high levels of CCR10 receptor, in herpes-infected asymptomatic (ASYMP) women compared to symptomatic (SYMP) women. A significant amount of the CCL28 chemokine (a ligand of CCR10), was detected in the VM of herpes-infected ASYMP B6 mice, associated with the mobilization of high frequencies of HSV-specific effector memory CCR10⁺CD44⁺ CD62L^- CD8⁺ T_EM cells and memory CCR10⁺B220⁺CD27⁺ B cells in the VM of HSV-infected asymptomatic mice. In contrast, compared to wild-type (WT) B6 mice, the CCL28 knockout (CCL28^(-/-)) mice: (i) Appeared more susceptible to intravaginal infection and re-infection with HSV-2; (ii) Exhibited a significant decrease in the frequencies of HSV-specific effector memory CCR10⁺CD44⁺ CD62L^- CD8⁺ T_EM cells and of memory CD27⁺B220⁺ B cells in the infected VM. The results imply a critical role of the CCL28/CCR10 chemokine axis in the mobilization of anti-viral memory B and T cells within the VM to protect against genital herpes infection and disease.

Keywords: CCL28; HSV-2; genital herpes; memory B cells; memory CD8+ T cells; mucosa.

Publication types

Preprint