Loading...
The Role of PD-1 and Its Ligands in Mercury(Hg)-induced Autoimmunity
Piaggio, Eduardo
Piaggio, Eduardo
Citations
Altmetric:
Genre
Thesis/Dissertation
Date
2009
Advisor
Group
Department
Microbiology and Immunology
Permanent link to this record
Collections
Research Projects
Organizational Units
Journal Issue
DOI
http://dx.doi.org/10.34944/dspace/2137
Abstract
The development of autoimmune diseases is frequently linked to exposure to environmental factors such as chemicals, drugs or infections. In the experimental model of metal-induced autoimmunity, administration of subtoxic doses of mercury (a common environmental pollutant) to genetically susceptible mice induces an autoimmune syndrome with rapid anti-nucleolar antibody production and immune system activation. Regulatory components of the innate immune system such as the costimulatory molecules PD-1, CTLA-4 and their ligands PD-L1, PD-L2, B7-1 and B7-2 can also modulate the autoimmune process. We examined the interplay among environmental chemicals and these costimulatory molecules in the regulation of autoimmunity. Additionally, we studied PD-1, CTLA-4 and its ligands in a tolerance model where pre-administration of a low dose of mercury in the steady state renders animals tolerant to metal-induced autoimmunity. Overall, PD-1/CTLA-4 blockade by blocking antibodies enhanced the manifestations of metal-induced autoimmunity. Although we expected that the blockade of both PD-1 ligands would mimic blocking the receptor, blocking the ligands resulted in the opposite effect when co-injected with mercury, reducing the manifestations of metal-induced autoimmunity. Individual PD-1 ligands differed in their ability to enhance the mercury treatment, with PD-L1 being the major regulator in the model. Likewise, we showed that PD-L1 is essential to keep the recall response to mercury at check. Our data suggest that these effects could be mediated by the modification of cytokine profiles, B cells and T cell subpopulations numbers.
Description
Citation
Citation to related work
Has part
ADA compliance
For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu