Treg Development and Suppression of Experimental Allergic Encephalomyelitis (129.28)

Autor: Cara Haymaker, Ping Yu, Jason Ellis, Rohit D Divekar, Renu Jain, Danielle Tartar, Hyun-Hee Lee, John Hardaway, Christine Hoeman, F. Betul Guloglu, Habib Zaghouani
Rok vydání: 2007
Předmět:
Zdroj: The Journal of Immunology. 178:S223-S223
ISSN: 1550-6606
0022-1767
Popis: Many autoimmune disorders have been linked to a lack in T regulatory cells. As such, an understanding of how these cells develop and mature is critical. While thymic T cell selection has been described, this process remains largely undefined for Tregs. Since only the DM20 form of proteolipid protein (PLP) is expressed in the thymus during fetal and neonatal life, thymic selection against PLP139-151 which is missing in DM20 is not operative during those periods. PLP139-151 (designated PLP1) as well as PLP1 derived altered peptide with degenerate affinity to PLP1-specific T cells were expressed on immunoglobulin (Ig) and the resulting chimeras were used to cross the maternal placenta, deliver the peptides from mother to fetus, and restore peptide selection during the fetal and neonatal period. This model was then used to determine whether Tregs are subject to thymic selection and to gauge the affinity required for such selection. The findings indicate that selection of functional Tregs requires high affinity. Indeed, Ig chimeras harboring high avidity peptides facilitated development of Tregs that conferred protection against experimental allergic encephalomyelitis (EAE) while chimeras incorporating low affinity peptide did not drive selection of Tregs and the animals remained susceptible to EAE.
Databáze: OpenAIRE