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A role of cellular prion protein in programming T‐cell cytokine responses in disease
Author(s) -
Ingram Rebecca J.,
Isaacs Jeremy D.,
Kaur Gurman,
Lowther Daniel E.,
Reynolds Catherine J.,
Boyton Rosemary J.,
Collinge John,
Jackson Graham S.,
Altmann Daniel M.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-116087
Subject(s) - t cell , experimental autoimmune encephalomyelitis , biology , immunology , context (archaeology) , il 2 receptor , cytokine , microbiology and biotechnology , immune system , paleontology
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‐α 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.—Ingram, R.J., Isaacs, J.D., Kaur, G., Lowther, D.E., Reynolds, C.J., Boyton,R. J., Collinge, J., Jackson, G.S., Altmann, D.M. A role of cellular prion protein in programming T‐cell cytokine responses in disease. FASEB J. 23, 1672–1684 (2009)