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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02075

Mucosal-pull induction of lung resident memory CD8 T cells in parenteral TB vaccine-primed hosts requires cognate antigens and CD4 T cells

 Zhou Xing1*,  Siamak Haddadi1, Maryam Vaseghi-Shanjani1, Yushi Yao1, Sam Afkhami1,  Michael D'Agostino1, Anna Zganiacz1 and Mangalakumari Jeyanathan1
  • 1McMaster University, Canada

Tissue resident memory T cells (TRM) are critical to host defense at mucosal tissue sites. However, the parenteral route of immunization as the most commonly used immunization route in practice is not effective in inducing mucosal TRM cells particularly in the lung. While various respiratory mucosal (RM)-pull strategies are exploited to mobilize parenteral vaccine-primed T cells into the lung, whether such RM pull strategies can all or differentially induce Ag-specific TRM cells in the lung remains unclear. Here we have addressed this issue by using a parenteral TB vaccine-prime and RM-pull model. We show that both Ag-independent and Ag-dependent RM pull strategies are able to mobilize Ag-specific CD8 T cells into the lung. However, only the RM pull strategy with cognate antigens can induce robust Ag-specific CD8 TRM cells in the lung. We also show that the cognate Ag-based RM pull strategy is the most effective in inducing TRM cells when carried out during the memory phase, as opposed to the effector phase, of T cell responses to parenteral prime vaccination. We further find that cognate Ag-induced CD4 T cells play an important role in the development of CD8 TRM cells in the lung. Our study holds implications in developing effective vaccine strategies against respiratory pathogens.

Keywords: Tuberculosis, Lung, Vaccine, T cells, Prime-pull, Parenteral immunisation

Received: 21 Jun 2019; Accepted: 16 Aug 2019.

Copyright: © 2019 Xing, Haddadi, Vaseghi-Shanjani, Yao, Afkhami, D'Agostino, Zganiacz and Jeyanathan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Zhou Xing, McMaster University, Hamilton, Canada, xingz@mcmaster.ca