CD301b+ dendritic cells stimulate tissue-resident memory CD8+ T cells to protect against genital HSV-2
نویسندگان
چکیده
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.
منابع مشابه
Virus-Specific Immune Memory at Peripheral Sites of Herpes Simplex Virus Type 2 (HSV-2) Infection in Guinea Pigs
Despite its importance in modulating HSV-2 pathogenesis, the nature of tissue-resident immune memory to HSV-2 is not completely understood. We used genital HSV-2 infection of guinea pigs to assess the type and location of HSV-specific memory cells at peripheral sites of HSV-2 infection. HSV-specific antibody-secreting cells were readily detected in the spleen, bone marrow, vagina/cervix, lumbos...
متن کاملMucosal HSV-2 Specific CD8+ T-Cells Represent Containment of Prior Viral Shedding Rather than a Correlate of Future Protection
It is largely unknown why certain infected hosts shed Herpes Simplex Virus-2 (HSV-2) more frequently and have more severe disease manifestations than others. One idea is that different density or functional capacity of tissue resident effector memory CD8+ T-cells between infected persons may explain phenotypic variability. To generate hypotheses for contrasting shedding patterns in different in...
متن کاملCXCR3 deficiency increases susceptibility to genital herpes simplex virus type 2 infection: Uncoupling of CD8+ T-cell effector function but not migration.
CXCR3 is a G-protein-coupled receptor preferentially expressed by activated T cells, NK cells, and dendritic cells. Signaling through gamma interferon-regulated chemokines CXCL9, CXCL10, CXCL11, and CXCR3 plays a critical role in the immune response of many viral pathogens. However, the relevance of CXCR3 for optimal T-cell activation and the induction of regulatory transcription factors (i.e.,...
متن کاملDifferential roles of migratory and resident DCs in T cell priming after mucosal or skin HSV-1 infection
Although mucosal surfaces represent the main portal of entry for pathogens, the mechanism of antigen presentation by dendritic cells (DCs) that patrol various mucosal tissues remains unclear. Instead, much effort has focused on the understanding of initiation of immune responses generated against antigens delivered by injection. We examined the contributions of migratory versus lymph node-resid...
متن کاملOverexpression of interleukin-15 compromises CD4-dependent adaptive immune responses against herpes simplex virus 2.
Interleukin-15 (IL-15) is necessary for the development and function of NK/NKT cells and the maintenance of naive and memory CD8(+) T cells. In the absence of IL-15, protective innate immunity is not available; however, a functional adaptive immune response against vaginal herpes simplex virus 2 (HSV-2) is generated. Mice overexpressing IL-15 (IL-15tg mice) have higher numbers of NK cells, grea...
متن کامل