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.
Highlights
Tissue-resident memory CD8 þ T (CD8 tissue-resident memory (TRM)) cells are an essential component of protective immune responses at barrier tissues, including the female genital tract
In the prime and pull model, there is minimal increase in the number of CD8 þ T cells in the vagina after challenge for the first 40 h post infection (Supplementary Fig. 1). This suggests that CD8 TRM cells in the vagina responding to herpes simplex virus (HSV) do not recruit circulating CD8 þ T cells[9] in the first couple of days of infection. These results indicate that circulating memory CD8 þ T cells are largely dispensable for defence against disease caused by genital HSV-2 infection, and that CD8 TRM cells in the vagina are sufficient to mediate early protection
As the majority of CD301b þ dendritic cells (DCs) are situated in the lamina propria, we examined whether CD8 TRM cells and CD301b þ DCs could interact in the event of an HSV-2 infection
Summary
Tissue-resident memory CD8 þ T (CD8 TRM) cells are an essential component of protective immune responses at barrier tissues, including the female genital tract. CD8 TRM cells are a newly described subset that survey both lymphoid and non-lymphoid tissues independently of circulating populations of memory CD8 T cells[1] Owing to their stable localization in most barrier tissues such as the genital tract, CD8 TRM are uniquely suited for rapid immune responses to pathogens that invade the host through those tissues. After a primary infection with herpes simplex virus (HSV)-2, migrant CD11b þ CD205 þ DC from the vagina stimulate naive T-cell responses within the draining lymph node (dLN)[22,23] In immunized mice, both DCs and B cells contribute to the activation of memory CD4 þ T cells in the vagina[24]. Control of infection at barrier surfaces such as the genital tract requires local immune responses at the tissue site to effectively limit spread of the pathogen
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