NR AOPX
AU Ballerini,C.; Chardonnet,S.; Metharom,P.; Aucouturier,P.; Carnaud,C.
TI Possible role of cellular prion protein in the immune system
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-107
PT Konferenz-Poster
AB
The fact that a same protein may perform mutiple functions within a given physiological system or in different systems is not uncommon. Recently it has been shown that neurons expressed an unusual number of molecules that were originally thought to be specific of immune functions.
The cellular isoform of PrP (PrPc), essential in the pathogenesis of TSE, is an ubiquitous host protein, with a predominant expression in the brain and in mononucleated cells of blood and lymphoid tissues. The exact function of PrPc is still unknown. In the CNS, PrPc seems involved in synaptic transmission, survival of neuronal cells and sleep behaviour. In peripheral blood leucocytes, on the other hand, PrPc expression correlates with activation and developmental status of various subsets including T lymphocytes and dendritic cells (DC).
On the bases of those observations, we have presently explored the possibility that PrPc might be involved in the specific interactions between T lymphocytes and bone-marrow derived DC, during antigen presentation and T cell activation. Two slightly different models of immunological synapse have been developed for this purpose: classical MLR with an MHC disparity and syngenic T/DC interaction following T cell activation with low concentrations of anti-CD3 antibodies. Readouts were T cell proliferation, expression of activation markers (CD25 and CD69) and lymphokine release. The results point clearly at an involvement of PrPc on both sides of the synapse. Absence of PrPc expression on either partner results in a less efficient response, and anti-PrP antibodies block, in a dose dependent fashion, the activation process. Further studies will try to elucidate the precise nature of this interaction, the molecular events that are linked to it and the more general consequences of a lack of PrPc signalling on the immune responses.
AD Clara Ballerini, INSERM E209, Paris France; Solenne Chardonnet, Pat Metharom, Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Brisbane, Queensland 4029, Australia; Pierre Aucouturier (aucouturier@necker.fr), Institut National de la Sante et de la Recherche Medicale (INSERM) U25 and Centre National de la Recherche Scientifique U8603, Hopital Necker, Paris, France; Claude Carnaud (carnaud@necker.fr), Institut National de la Sante et de la Recherche Medicale Unite 25, Hopital Necker, Paris, France
SP englisch
PO Deutschland