Rapid immunosurveillance by recirculating lymphocytes in the rat intestine: critical role of unsulfated sialyl-Lewis X on high endothelial venules of the Peyer’s patches

Uchida, Tomomi; Ueta, Hisashi; Xu, Xuedong; Hirakawa, Jotaro; Tahara, Kazunori; Shu, Zhao; Sawanobori, Yasushi; Simmons, Szandor; Kitazawa, Yoshiaki; Kawashima, Hiroto; Matsuno, Kenjiro

doi:10.1093/intimm/dxx072

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“…For dose response, we employed thoracic duct lymphocytes (TDLs) as a convenient source of donor lymphocytes, which were functionally almost the same as those in the blood (25, 26). At least 3 × 10 5 T cells from donor TDLs, representing those in ~100 μl of blood, induced significant DST antibody production (Figure 1D).…”

Section: Resultsmentioning

confidence: 99%

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Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes

et al. 2019

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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-asialoGM 1 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.

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Section: Resultsmentioning

confidence: 99%

“…When normal TDLs of congeneric PVG/c RT7 b rats are transferred to PVG/c RT7 a rats, they enter the PALS, although not being activated by the DCs (27). Even allogeneic naïve T cells can do so in similar kinetics to that of congeneic T cells (Figure 2) (25–27), thus providing a chance to deliver alloantigen to recipient DCs.…”

Section: Discussionmentioning

confidence: 96%

Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes

et al. 2019

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Rapid immunosurveillance by recirculating lymphocytes in the rat intestine: critical role of unsulfated sialyl-Lewis X on high endothelial venules of the Peyer’s patches

Abstract: Lymphocytes can transfer from blood to lymph or respond to antigen in Peyer’s patches

Cited by 1 publication

References 29 publications

Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes

Novel Targeting to XCR1+ Dendritic Cells Using Allogeneic T Cells for Polytopical Antibody Responses in the Lymph Nodes

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