Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28058717
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Eur+J+Immunol
2017 ; 47
(3
): 458-469
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Deletional tolerance prevents AQP4-directed autoimmunity in mice
#MMPMID28058717
Vogel AL
; Knier B
; Lammens K
; Kalluri SR
; Kuhlmann T
; Bennett JL
; Korn T
Eur J Immunol
2017[Mar]; 47
(3
): 458-469
PMID28058717
show ga
Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous
system (CNS) mediated by antibodies to the water channel protein AQP4 expressed
in astrocytes. The contribution of AQP4-specific T cells to the class switch
recombination of pathogenic AQP4-specific antibodies and the inflammation of the
blood-brain barrier is incompletely understood, as immunogenic naturally
processed T-cell epitopes of AQP4 are unknown. By immunizing Aqp4(-/-) mice with
full-length murine AQP4 protein followed by recall with overlapping peptides, we
here identify AQP4(201-220) as the major immunogenic IA(b) -restricted epitope of
AQP4. We show that WT mice do not harbor AQP4(201-220)-specific T-cell clones in
their natural repertoire due to deletional tolerance. However, immunization with
AQP4(201-220) of Rag1(-/-) mice reconstituted with the mature T-cell repertoire
of Aqp4(-/-) mice elicits an encephalomyelitic syndrome. Similarly to the T-cell
repertoire, the B-cell repertoire of WT mice is "purged" of AQP4-specific B
cells, and robust serum responses to AQP4 are only mounted in Aqp4(-/-) mice.
While AQP4(201-220)-specific T cells alone induce encephalomyelitis, NMO-specific
lesional patterns in the CNS and the retina only occur in the additional presence
of anti-AQP4 antibodies. Thus, failure of deletional T-cell and B-cell tolerance
against AQP4 is a prerequisite for clinically manifest NMO.
free
free
free
