T-lymphocyte activation and the cellular form of the prion protein.
The transmissible spongiform encephalopathies are neurodegenerative disorders which include Creutzfeldt-Jakob disease in humans, and scrapie and bovine spongiform encephalopathy in animals. A major component of the infectious agent responsible for these diseases is considered to be a post-translationally modified form of a host-encoded glycoprotein PrPc, termed PrPSc. While PrPc is abundantly expressed in tissues of the central nervous system (CNS), little is known about its normal function. The expression of PrPc is not restricted to the CNS, as this protein can also be detected in the lymphoid tissues of mice and sheep. In this report we demonstrate that resting murine splenic lymphocytes express PrPc protein on their cell membranes. Furthermore, expression of PrPc was significantly enhanced following in vitro stimulation with the non-specific T-cell mitogen concanavalin A (Con A). Genetically engineered mice with an inactive PrPc gene (PrP-/- mice), were utilized to investigate the involvement of PrPc in lymphocyte activation. Experiments revealed that the Con A-induced proliferation of lymphocytes from PrP-/- mice was significantly reduced to approximately 50-80% that of wild-type (PrP+/+) mice 48 hr post-stimulation. These findings demonstrate an important role for PrPc in extra-neuronal tissues and suggest that PrPc is a lymphocyte surface molecule that participates in T-cell activation.
Mabbott
N A
NA
Institute for Animal Health, Edinburgh, UK.
Brown
K L
KL
Manson
J
J
Bruce
M E
ME
D000818:Animals; D018929:Cell Culture Techniques; D002455:Cell Division / Q000276:immunology; D003208:Concanavalin A / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011328:Prions / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D011328:Prions; D003208:Concanavalin A