Gastric subserous vaccination with helicobacter pylori vaccine: An attempt to establish tissue-resident CD4+ memory T cells and induce prolonged protection
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2019Journal
Frontiers in ImmunologyPublisher
Frontiers Media S.A.Type
Article
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Tissue-resident memory T (Trm) cells are enriched at the sites of previous infection and required for enhanced protective immunity. However, the emergence of Trm cells and their roles in providing protection are unclear in the field of Helicobacter pylori (H. pylori) vaccinology. Here, our results suggest that conventional vaccine strategies are unable to establish a measurable antigen (Ag)-specific memory cell pool in stomach; in comparison, gastric subserous injection of mice with micro-dose of Alum-based H. pylori vaccine can induce a pool of local CD4+ Trm cells. Regional recruitment of Ag-specific CD4+ T cells depends on the engagement of Ag and adjuvant-induced inflammation. Prior subcutaneous vaccination enhanced this recruitment. A stable pool of Ag-specific CD4+ T cells can be detected for 240 days. Two weeks of FTY720 administration in immune mice suggests that these cells do not experience the recirculation. Immunohistochemistry results show that close to the vaccination site, abundant CD4+T cells locate on epithelial niches, independent of lymphocyte cluster. Paradigmatically, Ag-specific CD4+ T cells with a phenotype of CD69+CD103- are preferential on lymphocytes isolated from epithelium. Upon Helicobacter infection, CD4+ Trm cells orchestrate a swift recall response with the recruitment of circulating antigen-specific Th1/Th17 cells to trigger a tissue-wide pathogen clearance. This study investigates the vaccine-induced gastric CD4+ Trm cells in a mice model, and highlights the need for designing a vaccine strategy against H. pylori by establishing the protective CD4+ Trm cells. Copyright Copyright 2019 The Authors.Sponsors
This research was sponsored by the National key R&D Program of China (No. 2017YFD0400303), National Natural Science Foundation of China (No. 81502970), the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions and Postgraduate Research & Practice Innovation Program of Jiangsu Province.Keyword
CD4+ T cellsHelicobacter pylori
Immunological memory
Subunit vaccine
Tissue-resident memory T cells
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https://www.scopus.com/inward/record.uri?eid=2-s2.0-85067109886&doi=10.3389%2ffimmu.2019.01115&partnerID=40&md5=07425a0e26165f4d890b36970e31f1bb; http://hdl.handle.net/10713/10640ae974a485f413a2113503eed53cd6c53
10.3389/fimmu.2019.01115
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