Abstract
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 language | English |
|---|---|
| Pages (from-to) | 1549-1560 |
| Number of pages | 12 |
| Journal | Arthritis and Rheumatism |
| Volume | 50 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2004 |
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ASJC Scopus subject areas
- Immunology
- Rheumatology
Cite this
Requirement of Dying Cells and Environmental Adjuvants for the Induction of Autoimmunity. / Bondanza, Attilio; Zimmermann, Valérie S.; Dell'Antonio, Giacomo; Dal Cin, Elena; Balestrieri, Genesio; Tincani, Angela; Amoura, Zahir; Piette, Jean Charles; Sabbadini, Maria Grazia; Rovere-Querini, Patrizia; Manfredi, Angelo A.
In: Arthritis and Rheumatism, Vol. 50, No. 5, 05.2004, p. 1549-1560.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Requirement of Dying Cells and Environmental Adjuvants for the Induction of Autoimmunity
AU - Bondanza, Attilio
AU - Zimmermann, Valérie S.
AU - Dell'Antonio, Giacomo
AU - Dal Cin, Elena
AU - Balestrieri, Genesio
AU - Tincani, Angela
AU - Amoura, Zahir
AU - Piette, Jean Charles
AU - Sabbadini, Maria Grazia
AU - Rovere-Querini, Patrizia
AU - Manfredi, Angelo A.
PY - 2004/5
Y1 - 2004/5
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=2342499804&partnerID=8YFLogxK
U2 - 10.1002/art.20187
DO - 10.1002/art.20187
M3 - Article
VL - 50
SP - 1549
EP - 1560
JO - Arthritis care and research : the official journal of the Arthritis Health Professions Association
JF - Arthritis care and research : the official journal of the Arthritis Health Professions Association
SN - 0893-7524
IS - 5
ER -