The immunobiology of PrPc protein

Phenotypic studies of mice with altered levels of PrPc expression showed differences in lymphocyte subset composition of peripheral lymphoid tissue. Mice with a complete absence of PrPc expression showed a reduction in mononuclear cell numbers in lymphoid tissue compared to wild type mice. FACS analysis of these cells from mice that expressed different levels of PrPc revealed no difference in subset composition. Similarly, the dendritic cell composition of lymphoid tissue was similar in animals with different levels of PrPc expression. The mitogenic responses of PrP+/+ lymphocytes were greater in magnitude compared to equivalent PrP-/- cells. In-vivo activated lymphocytes from Fas-/- mice showed an increase in cell surface PrPc expression compared to wild type cells. Similarly, PrPc expression was increased on in-vitro activated cells. These data indicated a role for PrPc in lymphocyte proliferation. However, anti-PrP monoclonal antibodies failed to inhibit the proliferation of mitogen-stimulated cells. when an immune response to inert protein antigen was compared in mice with different levels of PrPc expression, antibody isotype levels were similar in PrP-/- and PrP+/+ mice. However, when live virus challenge with HSV-1 was investigated PrP-/- mice had a reduced viral titre compared to wild type indicating that PrPc expression plays an important role in immune responses to viral pathogens. Inoculation of wild type mice with recombinant PrPc in Complete Freund’s adjuvant showed retardation of onset of prion disease, which indicated that tolerance to PrPc could be circumvented.EThOS - Electronic Theses Online ServiceGBUnited Kingdo