| First Author | Ingram RJ | Year | 2009 |
| Journal | FASEB J | Volume | 23 |
| Issue | 6 | Pages | 1672-84 |
| PubMed ID | 19204074 | Mgi Jnum | J:150549 |
| Mgi Id | MGI:3850935 | Doi | 10.1096/fj.08-116087 |
| Citation | Ingram RJ, et al. (2009) A role of cellular prion protein in programming T-cell cytokine responses in disease. FASEB J 23(6):1672-84 |
| abstractText | The cellular prion protein (PrP(C)) is widely expressed in neural and non-neural tissues, but its function is unknown. Elucidation of the part played by PrP(C) in adaptive immunity has been a particular conundrum: increased expression of cell surface PrP(C) has been documented during T-cell activation, yet the functional significance of this activation remains unclear, with conflicting data on the effects of Prnp gene knockout on various parameters of T-cell immunity. We show here that Prnp mRNA is highly inducible within 8-24 h of T-cell activation, with surface protein levels rising from 24 h. When measured in parallel with CD69 and CD25, PrP(C) is a late activation antigen. Consistent with its up-regulation being a late activation event, PrP deletion did not alter T-cell-antigen presenting cell conjugate formation. Most important, activated PrP(0/0) T cells demonstrated much reduced induction of several T helper (Th) 1, Th2, and Th17 cytokines, whereas others, such as TNF-alpha and IL-9, were unaffected. These changes were investigated in the context of an autoimmune model and a bacterial challenge model. In experimental autoimmune encephalomyelitis, PrP-knockout mice showed enhanced disease in the face of reduced IL-17 responses. In a streptococcal sepsis model, this constrained cytokine program was associated with poorer local control of infection, although with reduced bacteremia. The findings indicate that PrP(C) is a potentially important molecule influencing T-cell activation and effector function. |
