Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes
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 sig...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01195/full |
| _version_ | 1818294339325919232 |
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| author | Yusuke Kitazawa Hisashi Ueta Yasushi Sawanobori Tomoya Katakai Hiroyuki Yoneyama Satoshi Ueha Kouji Matsushima Nobuko Tokuda Kenjiro Matsuno |
| author_facet | Yusuke Kitazawa Hisashi Ueta Yasushi Sawanobori Tomoya Katakai Hiroyuki Yoneyama Satoshi Ueha Kouji Matsushima Nobuko Tokuda Kenjiro Matsuno |
| author_sort | Yusuke Kitazawa |
| collection | DOAJ |
| description | 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 vs. 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 (SLOs) 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. |
| first_indexed | 2024-12-13T03:30:11Z |
| format | Article |
| id | doaj.art-c1c18ae551c54cc9a72c1d641352e0d2 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T03:30:11Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c1c18ae551c54cc9a72c1d641352e0d22022-12-22T00:01:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-05-011010.3389/fimmu.2019.01195429784Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph NodesYusuke Kitazawa0Hisashi Ueta1Yasushi Sawanobori2Tomoya Katakai3Hiroyuki Yoneyama4Satoshi Ueha5Kouji Matsushima6Nobuko Tokuda7Kenjiro Matsuno8Department of Anatomy (Macro), School of Medicine, Dokkyo Medical University, Tochigi, JapanDepartment of Anatomy (Macro), School of Medicine, Dokkyo Medical University, Tochigi, JapanDepartment of Anatomy (Macro), School of Medicine, Dokkyo Medical University, Tochigi, JapanDepartment of Immunology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, JapanTME Therapeutics Inc., Tokyo, JapanDivision of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, JapanDivision of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, JapanDepartment of Anatomy (Macro), School of Medicine, Dokkyo Medical University, Tochigi, JapanDepartment of Anatomy (Macro), School of Medicine, Dokkyo Medical University, Tochigi, JapanVaccination 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 vs. 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 (SLOs) 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.01195/fulldendritic cell targetingallogeneic T cellvaccinationaspleniapolytopical antibody productionlymph nodes |
| spellingShingle | Yusuke Kitazawa Hisashi Ueta Yasushi Sawanobori Tomoya Katakai Hiroyuki Yoneyama Satoshi Ueha Kouji Matsushima Nobuko Tokuda Kenjiro Matsuno Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes Frontiers in Immunology dendritic cell targeting allogeneic T cell vaccination asplenia polytopical antibody production lymph nodes |
| title | Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes |
| title_full | Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes |
| title_fullStr | Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes |
| title_full_unstemmed | Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes |
| title_short | Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes |
| title_sort | novel targeting to xcr1 dendritic cells using allogeneic t cells for polytopical antibody responses in the lymph nodes |
| topic | dendritic cell targeting allogeneic T cell vaccination asplenia polytopical antibody production lymph nodes |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01195/full |
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