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Critical role of macrophages in the marginal zone in the suppression of immune responses to apoptotic cell–associated antigens
Yasunobu Miyake, … , Manabu Nakayama, Masato Tanaka
Yasunobu Miyake, … , Manabu Nakayama, Masato Tanaka
Published August 1, 2007
Citation Information: J Clin Invest. 2007;117(8):2268-2278. https://doi.org/10.1172/JCI31990.
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Research Article Immunology Article has an altmetric score of 9

Critical role of macrophages in the marginal zone in the suppression of immune responses to apoptotic cell–associated antigens

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Abstract

Injection of apoptotic cells can induce suppression of immune responses to cell-associated antigens. Here, we show that intravenous injection of apoptotic cells expressing a fragment of myelin oligodendrocyte glycoprotein (MOG) reduced MOG-specific T cell response and prevented the development of EAE. Since injected apoptotic cells accumulated initially in the splenic marginal zone (MZ), the role of macrophages in the MZ in immune suppression was examined using transgenic mice in which these cells could be transiently deleted by diphtheria toxin (DT) injection. DT-treated mice became susceptible to EAE even though MOG-expressing apoptotic cells were preinjected. Deletion of the macrophages caused delayed clearance of injected dying cells in the MZ. In wild-type mice, injected apoptotic cells were selectively engulfed by CD8α+ DCs, which are responsible for suppression of immune responses to cell-associated antigens. In contrast, deletion of macrophages in the MZ caused aberrant phagocytosis of injected dying cells by CD8α–CD11b+ DCs. These results indicate that macrophages in the MZ regulate not only efficient clearance of apoptotic cells but also selective engulfment of dying cells by CD8α+ DCs and that functional failure of these unique macrophages impairs suppression of immune responses to cell-associated antigens.

Authors

Yasunobu Miyake, Kenichi Asano, Hitomi Kaise, Miho Uemura, Manabu Nakayama, Masato Tanaka

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Figure 3

Administration of apoptotic W3/MOG cells induced antigen-specific T cell unresponsiveness.

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Administration of apoptotic W3/MOG cells induced antigen-specific T cell...
(A and B) We intravenously injected 2 × 107 apoptotic W3/MOG-L cells into mice. Three days later, 100 μg of MOG35–55 (A) or KLH (B) in CFA was injected subcutaneously into the bilateral foot pads. Popliteal and inguinal LNs were collected from the mice 5 days after immunization. In vitro, 5 × 105 LN cells were restimulated with MOG35–55 (A) or KLH (B) for 70 hours. T cell proliferation was quantified based on the [3H] thymidine uptake in the last 20 hours of the culture. Mean values are shown with SD. Numbers indicate mouse 1 and mouse 2. (C and D) Apoptotic W3/MOG-L cell injection reduces IFN-γ and IL-17 production in splenocytes. We intravenously injected 2 × 107 apoptotic W3 or W3/MOG-L cells into mice 4 days prior to immunization of MOG35–55 on day 0. Splenocytes obtained 10 days after immunization were restimulated in vitro with MOG35–55 for 72 hours. Production of IFN-γ (C) and IL-17 (D) was measured by ELISA. Mean values are shown with SEM. *P < 0.05. These results are representative of 3 independent experiments.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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