title: Role of CD40 in prion disease and the immune response to recombinant PrP.
abstract: The CD40 receptor-CD40 ligand (CD40-CD40L) interaction has been shown to affect both immune and non-immune cells and is implicated in diverse activities including immunoglobulin class switching (IgM to IgG), atherosclerosis, chronic inflammation and Alzheimer's disease pathogenesis. A number of groups have studied the role of CD40 in prion disease, however, the results are conflicting presumably due to the use of different scrapie agent-host strain combinations and routes of infection. In the current study, we clarify the effect of CD40 on: (i) replication, progression to clinical disease, PrP(Sc) profile, and neuropathology associated with infection of a single host genotype with three distinct mouse-adapted scrapie strains, and (ii) the immune response of double knockout (PrP, CD40) transgenic mice to recombinant PrP as assessed by the generation of anti-PrP antibodies. Our results suggest that CD40: (i) results in slower disease progression and scrapie strain-specific differences in incubation periods, (ii) does not affect the level of scrapie strain-specific PrP(Sc), (iii) does not influence disease-associated neuropathology, but (iv), as expected, is required to mount an immune response generating anti-PrP IgG antibodies.
authors: Department of Neurology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA. richard.rubenstein@downstate.edu
authors: Richard
authors: R
authors: Rubenstein
authors: Allen
authors: A
authors: Chiu
authors: Binggong
authors: B
authors: Chang
authors: Thomas
authors: T
authors: Wisniewski
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017096:Prion Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011328:Prions / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D011328:Prions; D011994:Recombinant Proteins