Induction of vaginal-resident HIV-specific CD8 T cells with mucosal prime-boost immunization

Tissue-resident memory (T ) CD8 T cells survey a range of non-lymphoid mucosal tissues where they rapidly mediate clearance of viral infections at the entry portals. Vaccines that establish CD8 T cells in the cervicovaginal mucosa hold promise for effective immunity against sexually transmitted HIV....

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Bibliographic Details
Published in:Mucosal immunology 2018-05, Vol.11 (3), p.994-1007
Main Authors: Tan, H-X, Wheatley, A K, Esterbauer, R, Jegaskanda, S, Glass, J J, Masopust, D, De Rose, R, Kent, S J
Format: Article
Language:English
Subjects:
Adaptive Immunity
AIDS Vaccines - immunology
Animals
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cell Movement
Endothelium, Vascular - physiology
Female
Genetic Vectors
HIV
HIV Infections - immunology
HIV-1 - immunology
Human immunodeficiency virus
Humans
Immune clearance
Immune system
Immunization
Immunization, Secondary
Immunofluorescence
Immunologic Memory
Immunological memory
Influenza
Influenza, Human - genetics
Localization
Lymphocyte Activation
Lymphocytes
Lymphocytes T
Memory cells
Mice
Mice, Inbred BALB C
Mucosa
Mucous Membrane - immunology
Mucous Membrane - virology
Organ Specificity
Vagina
Vagina - immunology
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Summary:Tissue-resident memory (T ) CD8 T cells survey a range of non-lymphoid mucosal tissues where they rapidly mediate clearance of viral infections at the entry portals. Vaccines that establish CD8 T cells in the cervicovaginal mucosa hold promise for effective immunity against sexually transmitted HIV. We demonstrate that HIV-specific CD8 T cells can be established in the murine vaginal mucosa using a combined intranasal and intravaginal mucosal immunization with recombinant influenza-HIV vectors. Using in situ tetramer immunofluorescence microscopy, we found that this mucosally administered prime-boost immunization also resulted in the durable seeding of CD8 T cells in the frontline vaginal epithelial compartment as opposed to the vaginal submucosa. Upon cognate antigen recognition within the vaginal mucosa, these HIV-specific CD8 T cells rapidly initiated a tissue-wide state of immunity. The activation of HIV-specific CD8 T cells resulted in the upregulation of endothelial vessel addressin expression and substantial recruitment of both adaptive and innate immune cells in the vaginal mucosa. These findings suggest that the epithelial localization of HIV-specific CD8 T cell populations and their capacity to rapidly activate both arms of the immune system could significantly augment frontline defenses against vaginal HIV infection.
ISSN:1933-0219
1935-3456
DOI:10.1038/mi.2017.89