CD301b+ dendritic cells stimulate tissue-resident memory CD8+ T cells to protect against genital HSV-2

Abstract

Tissue-resident memory CD8+ T (CD8 TRM) cells are an essential component of protective immune responses at barrier tissues, including the female genital tract. However, the mechanisms that lead to the initiation of CD8 TRM-mediated protective immunity after viral infection are unclear. Here we report that CD8 TRM cells established by ‘prime and pull' method confer protection against genital HSV-2 infection, and that IFN-γ produced by CD8 TRM cells is required for this protection. Furthermore, we find that CD8 TRM-cell restimulation depends on a population of CD301b+ antigen-presenting cells (APC) in the lamina propria. Elimination of MHC class I on CD301b+ dendritic cells abrogates protective immunity, suggesting the requirement for cognate antigen presentation to CD8 TRM cells by CD301b+ dendritic cells. These results define the requirements for CD8 TRM cells in protection against genital HSV-2 infection and identify the population of APC that are responsible for activating these cells.

Aging impacts CD103+CD8+ T cell presence and induction by dendritic cells in the genital tract

“…Recent murine studies demonstrate that memory CD103 + CD8 + T cells in the nasal mucosa prevent dissemination of pulmonary influenza virus infection to the lungs (Pizzolla et al., 2017). Animal studies have also demonstrated that TRMs mediate local protection against genital HSV‐2 infections (Shin, Kumamoto, Gopinath & Iwasaki, 2016). Therefore, induced immune cell protection against STIs in humans would likely require a potent resident memory T‐cell population (Iwasaki, 2010).…”

“…As women age and remain sexually active, protection of the FRT at all ages is essential. Our findings are particularly relevant to HIV prevention, because most CD8 + T cell studies focus on the evaluation of blood T‐cell responses, which do not correlate with the protective effects of resident T cells in the FRT (Shin et al., 2016; White et al., 2001). …”

Tissue-Specific Control of Tissue-Resident Memory T Cells

“…102,103 CD301b + LP DCs are required to activate vaginal T RM s upon vaginal herpes virus re-challenge. 104 In contrast, dorsal root ganglia resident T RM s are re-activated by recruited monocyte-derived DCs 105 and skin CD8 + T RM s are reactivated by almost any directly infected epidermal cells carrying cognate antigens. 106 Recent results have demonstrated that FRT T RM cells undergo expansion and differentiation in situ during re-challenge.…”

“…Thus, in addition to a sentinel system, mucosal T RM function as a robust self-sufficient defense system and can function independent of circulating T cells. 104,107 …”

T cell metabolism in chronic viral infection

“…Tissue-resident memory T cells (T rm ) are compartmentalized away from the circulating pool via the expression of the tissue-retention signals CD69 and/or CD103 [58]. They can be directed against viruses that invade these sites: for example, HBV-specific CD8 + T rm have been found in the human liver [59], murine herpes simplex virus 1-specific T rm in the lamina propria of the vagina [60] and human influenza A-specific T cells in the lung [61]. CD8 + T rm provide rapid antigen-specific recall responses in situ and therefore act as highly functional defence specialists, with adaptations imposed by their local niche.…”