CD301b+ dendritic cells stimulate tissue-resident memory CD8+ T cells to protect against genital HSV-2.
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 TRMcells established by 'prime and pull' method confer protection against genital HSV-2 infection, and that IFN-γ produced by CD8 TRMcells 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 TRMcells by CD301b+dendritic cells. These results define the requirements for CD8 TRMcells in protection against genital HSV-2 infection and identify the population of APC that are responsible for activating these cells.
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520 USA.
Haina
H
Shin
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520 USA.
Yosuke
Y
Kumamoto
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520 USA.
Smita
0000-0003-3672-3780
S
Gopinath
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520 USA.|Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520 USA.
Akiko
0000-0002-7824-9856
A
Iwasaki
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology* / Q000628:therapy / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology* / Q000502:physiology; D007156:Immunologic Memory / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D014621:Vagina / Q000276:immunology / Q000821:virology
D037181:Lectins, C-Type; C464940:MGL2 protein, mouse