Requirement of Dying Cells and Environmental Adjuvants for the Induction of Autoimmunity

Attilio Bondanza, Valérie S. Zimmermann, Giacomo Dell'Antonio, Elena Dal Cin, Genesio Balestrieri, Angela Tincani, Zahir Amoura, Jean Charles Piette, Maria Grazia Sabbadini, Patrizia Rovere-Querini, Angelo A. Manfredi

Research output: Contribution to journalArticlepeer-review


Objective. Cells commonly die without eliciting autoimmunity. However, dying cells are a potential initiating stimulus for systemic lupus erythematosus (SLE). Our goal was to verify whether immune adjuvants influence the autoimmunity induction that ensues following in vivo injection of dying cells. Methods. Mice were immunized with apoptotic thymocytes in the presence of artificial moieties, such as Freund's incomplete adjuvant (IFA), or natural adjuvants, such as dendritic cells (DCs). Renal involvement and the development of autoantibodies were monitored. Results. Apoptotic cells failed to induce clinical disease or to sustain production of autoantibodies in (NZB x NZW)F 1 mice. In contrast, autoimmunity developed in the presence of IFA or DCs. The characteristics of the adjuvant influenced the array of autoantibodies, the kinetics of their development, and the severity of the disease. DCs were required for induction of anti-β 2-glycoprotein I IgG. Adjuvants alone did not elicit disease. Conclusion. A "two-hit" signal composed of autoantigens and adjuvants initiates systemic autoimmunity. Moreover, environmental signals at the site of clearance of dead cells shape the features and the severity of the autoimmune disease. Strategies aimed at preventing the accumulation of dying cells and at modulating endogenous adjuvants may be beneficial for the treatment of SLE.

Original languageEnglish
Pages (from-to)1549-1560
Number of pages12
JournalArthritis and Rheumatism
Issue number5
Publication statusPublished - May 2004

ASJC Scopus subject areas

  • Immunology
  • Rheumatology


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