組織内酸素濃度変化を背景とした子宮内膜再生における微小環境変化

臨時増刊1号東京女子医科大学医学部解剖学・発生生物学講座 講座主任 江﨑太一教授退任記念特別

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 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

Splenic differentiation and emergence of CCR5+CXCL9+CXCL10+ monocyte-derived dendritic cells in the brain during cerebral malaria

Dendritic cells have an important role in immune surveillance. After being exposed to microbial components, they migrate to secondary lymphoid organs and activate T lymphocytes. Here we show that during mouse malaria, splenic inflammatory monocytes differentiate into monocyte-derived dendritic cells (MO-DCs), which are CD11b+F4/80+CD11c+MHCIIhighDC-SIGNhighLy6c+ and express high levels of CCR5, CXCL9 and CXCL10 (CCR5+CXCL9/10+ MO-DCs). We propose that malaria-induced splenic MO-DCs take a reverse migratory route. After differentiation in the spleen, CCR5+CXCL9/10+ MO-DCs traffic to the brain in a CCR2-independent, CCR5-dependent manner, where they amplify the influx of CD8+ T lymphocytes, leading to a lethal neuropathological syndrome

Parvalbumin-positive Neurons in the Mouse A8 Region were Lesser than those in the Rat

Dopaminergic neurons play crucial roles in various physiological functions, such as reward, goal-directed behavior, memory formation, and pain sensation. One of the main dopaminergic cell groups in the brain is located in the retrorubral field (RRF, A8 region). A recent electrophysiological study using rats revealed that distinct neurons within the A8 region respond to the different degrees of the threat and aversive stimuli, and that the RRF is the origin of neural signals for threat and aversive outcomes. However, neurochemical characterization of the constituents of the A8 region is not enough. The aim of this study is to determine the neurochemical characteristics of these A8 neurons. To examine the neurochemical cellular organization of the A8 region, we performed immunohistochemistry for two GABAergic neuronal markers, parvalbumin (PV) and neuronal nitric oxide synthase (nNOS), in relation to tyrosine hydroxylase, a marker of dopaminergic neurons. We observed that the number of PV-positive neurons in the mouse A8 region was lesser than in rats. Moreover, nNOS-positive neurons were not detected within the A8 region in either species. These results indicate that the neurochemical organization of the A8 region was distinct between mice and rats. In addition, the cellular composition of the A8 dopaminergic cell group was distinct from other dopaminergic cell groups, such as the A9 and A10 region, in both mice and rats. Understanding these differences among species and cell groups is worth noting for translating the results obtained with distinct animal models into a clinical application