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

Front. Immunol. | doi: 10.3389/fimmu.2019.01195

Novel targeting to XCR1+ dendritic cells using allogeneic T cells for polytopical antibody responses in the lymph nodes

  • 1Department of Anatomy (Macro), Dokkyo Medical University, Japan
  • 2Department of Immunology, Graduate School of Medical and Dental Sciences, Niigata University, Japan
  • 3TME Therapeutics Inc, Japan
  • 4Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Japan

Vaccination strategy that induce efficient antibody responses polytopically in most lymph nodes (LNs) against infections has not been established yet. Because donor-specific blood transfusion induces anti-donor class I MHC antibody production in splenectomized rats, we examined the mechanism and significance of this response. Among the donor blood components, T cells were the most efficient immunogens, inducing recipient T cell and B cell proliferative responses not only in the spleen, but also in the peripheral and gut LNs. Donor T cells soon migrated to the splenic T cell area and the LNs, with a temporary significant increase in recipient NK cells. XCR1+ resident dendritic cells (DCs), but not XCR1– DCs, selectively phagocytosed donor class I MHC+ fragments after 1 day. After 1.5 days, both DC subsets formed clusters with recipient CD4+ T cells, which proliferated within these clusters. Inhibition of donor T cell migration or depletion of NK cells by pretreatment with pertussis toxin or anti-asialoGM1 antibody, respectively, significantly suppressed DC phagocytosis and subsequent immune responses. Three allogeneic strains with different NK activities had the same response but with different intensity. Donor T cell proliferation was not required, indicating that the graft versus host reaction is dispensable. Intravenous transfer of antigen-labeled and mitotic inhibitor-treated allogeneic, but not syngeneic, T cells induced a polytopical antibody response to labeled antigens in the LNs of splenectomized rats. These results demonstrate a novel mechanism of alloresponses polytopically in the secondary lymphoid organs induced by allogeneic T cells. Donor T cells behave as self-migratory antigen ferries to be delivered to resident XCR1+ DCs with negligible commitment of migratory DCs. Allogeneic T cells may be clinically applicable as vaccine vectors for polytopical prophylactic antibody production even in asplenic or hyposplenic individuals.

Keywords: Dendritic cell targeting, Allogeneic T cells, Vaccination, Asplenia, Lymph Nodes, XCR1+ dendritic cell, polytopical antibody production

Received: 09 Oct 2018; Accepted: 10 May 2019.

Edited by:

Irina Caminschi, Monash University, Australia

Reviewed by:

Ken Shortman, Walter and Eliza Hall Institute of Medical Research, Australia
Yu Kato, La Jolla Institute for Immunology (LJI), United States  

Copyright: © 2019 Kitazawa, Ueta, Sawanobori, Katakai, Yoneyama, Ueha, Matsushima, Tokuda and Matsuno. 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: Dr. Kenjiro Matsuno, Department of Anatomy (Macro), Dokkyo Medical University, Tochigi, Japan, kenjiro@dokkyomed.ac.jp