Reduced response of splenocytes after mitogen-stimulation in the prion protein (PrP) gene-deficient mouse: PrPLP/Doppel production and cerebral degeneration.
Splenocytes of wild-type (Prnp(+/+)) and prion protein gene-deficient (Prnp(-/-)) mice were treated with various activation stimuli such as T cell mitogen concanavalin A (ConA), phorbol 12-myristate 13-acetate (PMA)+ionomycin (Io), or B cell mitogen lipopolysaccharide (LPS). Cellular prion protein (PrP(C)) expression was enhanced following ConA stimulation, but not PMA+Io or LPS in Prnp(+/+) splenocytes. Rikn Prnp(-/-) splenocytes elicited lower cell proliferations than Prnp(+/+) or Zrch I Prnp(-/-) splenocytes after LPS stimulation and showed sporadic nerve cells in the cerebral cortex and deeper structure. Around the degenerated nerve cells, mild vacuolation in the neuropil was observed. This neural alteration correlated well to the suppressed response of B cells in the spleen. The finding that discrete lesions within the central nervous systems induced marked modulation of immune function probably indicates the existence of a delicately balanced neural-endocrine network by PrP(C) and PrPLP/Doppel.
Kim
Chi-Kyeong
CK
Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Tokyo, Japan.
Hirose
Yuko
Y
Sakudo
Akikazu
A
Takeyama
Natsumi
N
Kang
Chung-Boo
CB
Taniuchi
Yojiro
Y
Matsumoto
Yoshitsugu
Y
Itohara
Shigeyoshi
S
Sakaguchi
Suehiro
S
Onodera
Takashi
T
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D058851:GPI-Linked Proteins; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008934:Mitogens / Q000494:pharmacology*; D011328:Prions / Q000235:genetics / Q000378:metabolism*
D058851:GPI-Linked Proteins; D008934:Mitogens; D011328:Prions; C122036:Prnd protein, mouse