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

Y Miyake, K Asano, H Kaise, M Uemura… - The Journal of …, 2007 - Am Soc Clin Investig
Y Miyake, K Asano, H Kaise, M Uemura, M Nakayama, M Tanaka
The Journal of clinical investigation, 2007Am Soc Clin Investig
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 …
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 CD8αCD11b+ 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.
The Journal of Clinical Investigation