Visualizing mechanisms of peripheral tolerance against autoreactive T cells (129.35)

Autor: Rohit D. Divekar, Cara Haymaker, Renu Jain, Jason Ellis, Danielle Tartar, Ping Yu, Hyun-Hee Lee, John Hardaway, Christine Hoeman, Betul Guloglu, Craig Franklin, Mark Miller, Habib Zaghouani
Rok vydání: 2007
Předmět:
Zdroj: The Journal of Immunology. 178:S224-S224
ISSN: 1550-6606
0022-1767
Popis: Where and how T cell tolerance happens remains largely undefined. Here, we used an established in vivo model and investigated the site and the mechanisms that govern APC-mediated inactivation of autoreactive T cells. Fcγ receptor-deficient (FcγR−/−) mice were induced for experimental allergic encephalomyelitis (EAE), with a myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide and when the disease became apparent the mice were given FcγR+/+ APCs and treated with Ig-MOG, a tolerogenic Ig expressing MOG peptide. Under this regimen the mice were able to reverse their EAE only when given FcγR+/+ APCs that can present Ig-MOG and carry out T cell tolerance. This system was then used to visualize encounter of the APCs with the pathogenic T cells. The results indicate that tolerance occurs in a time dependent fashion when both the T cells and APCs have accumulated in sufficient number at the encounter site but unlike immunity, can take place in the non-draining lymph nodes. Two-Photon microscopy analysis revealed that tolerized T cells exhibit organ-specific changes in motility, pattern of migration and trafficking which could be related to functional matters as tolerance manifest the form of Th2 deviation in the lymph node and anergy in the spleen. Research supported by grant NS37406 from NIH.
Databáze: OpenAIRE