title: Annexin A1 on the surface of early apoptotic cells suppresses CD8+ T cell immunity.
abstract: Prevention of an immune response against self-antigens derived from apoptotic cells is essential to preclude autoimmune and chronic inflammatory diseases. Here, we describe apoptosis induced externalization of endogenous cytosolic annexin 1 initiating an anti-inflammatory effector mechanism that suppresses the immune response against antigens of apoptotic cells. Cytosolic annexin 1 rapidly translocated to the apoptotic cell surface and inhibited dendritic cell (DC) activation induced by Toll like receptors (TLR). Annexin 1-inhibited DC showed strongly reduced secretion of pro-inflammatory cytokines (e.g. TNF and IL-12) and costimulatory surface molecules (e.g. CD40 and CD86), while anti-inflammatory mediators like PD-L1 remained unchanged. T cells stimulated by such DC lacked secretion of interferon-γ (IFN-γ) and TNF but retained IL-10 secretion. In mice, annexin 1 prevented the development of inflammatory DC and suppressed the cellular immune response against the model antigen ovalbumin (OVA) expressed in apoptotic cells. Furthermore, annexin 1 on apoptotic cells compromised OVA-specific tumor vaccination and impaired rejection of an OVA-expressing tumor. Thus, our results provide a molecular mechanism for the suppressive activity of apoptotic cells on the immune response towards apoptotic cell-derived self-antigens. This process may play an important role in prevention of autoimmune diseases and of the immune response against cancer.
authors: Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany.
authors: Heiko
authors: H
authors: Weyd
authors: Lucie
authors: L
authors: Abeler-Dörner
authors: Björn
authors: B
authors: Linke
authors: Andrea
authors: A
authors: Mahr
authors: Veronika
authors: V
authors: Jahndel
authors: Sandra
authors: S
authors: Pfrang
authors: Martina
authors: M
authors: Schnölzer
authors: Christine S
authors: CS
authors: Falk
authors: Peter H
authors: PH
authors: Krammer
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000032:analysis / Q000276:immunology*; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: D017305:Annexin A1; D051193:Toll-Like Receptors
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