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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DOI：
10.3389/fimmu.2019.01195
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发表时间：
2019-05-29
影响因子：
7.3
通讯作者：
Matsuno, Kenjiro
中科院分区：
文献类型：
--
作者：
Kitazawa, Yusuke;Ueta, Hisashi;Matsuno, Kenjiro
在大多数淋巴结（LN）中诱导有效抗体应答的疫苗接种策略尚未建立。由于供体特异性输血诱导脾切除大鼠产生抗供体I类MHC抗体，我们研究了这种反应的机制和意义。在供体血液成分中，T细胞是最有效的免疫原，不仅在脾脏中，而且在外周和肠道淋巴结中诱导受体T细胞和B细胞增殖反应。供体T细胞很快迁移到脾T细胞区和淋巴结，受体NK细胞暂时显著增加。1天后，XCR 1（+）驻留树突状细胞（DC）而不是XCR 1（-）DC选择性吞噬供体I类MHC+片段。1.5天后，两个DC亚群与受体CD 4（+）T细胞形成簇，其在这些簇内增殖。分别用百日咳毒素或抗去唾液酸GM（1）抗体预处理，抑制供体T细胞迁移或消耗NK细胞，显著抑制DC吞噬作用和随后的免疫应答。三种NK活性不同的异基因株的免疫应答相同，但强度不同。不需要供体T细胞增殖，表明移植物抗宿主反应是不稳定的。静脉内转移的抗原标记和有丝分裂受体处理的同种异体，但不是同源的，T细胞诱导的多局部抗体反应标记的抗原在淋巴结的脾切除大鼠。这些结果证明了同种异体T细胞诱导的次级淋巴器官（SLO）多部位同种异体反应的新机制。供体T细胞表现为自我迁移的抗原渡船，被递送到驻留的XCR 1（+）DC，而迁移DC的承诺可忽略不计。同种异体T细胞可能在临床上适用于作为疫苗载体，用于即使在无脾或脾功能减退个体中的多局部预防性抗体产生。
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.