Treatment with intact anti-B7-1 mAb during disease remission enhances epitope spreading and exacerbates relapses in R-EAE.
PLP139-151-induced experimental autoimmune encephalomyelitis in the SJL mouse is a Th1-mediated inflammatory demyelinating disease characterized by a relapsing-remitting clinical course (R-EAE). Clinical relapses are mediated by T cells specific for a non-cross reactive secondary PLP epitope (PLP178-191) induced by epitope spreading. We have previously shown that B7-1 expression is upregulated in SJL mice undergoing R-EAE and in vivo treatment during remission with F(ab) fragments of anti-B7-1 mAb, blocked epitope spreading and disease progression. In contrast, the present study shows that treatment with intact anti-B7-1 mAb exacerbated clinical disease relapses and enhanced CNS demyelination. Anti-B7-1-treated mice showed enhanced in vivo delayed-type hypersensitivity (DTH) to the relapse-associated PLP178-191 epitope and responses to the immunodominant MBP84-104 epitope which are absent in the controls. Thus, ligation of B7-1 by intact mAbs has effects opposite to those of anti-B7-1 F(ab) fragments suggesting that the mAb is directly signaling through B7-1 expressed on T cells and/or APCs.
Vanderlugt
C L
CL
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611, USA.
Karandikar
N J
NJ
Lenschow
D J
DJ
Dal Canto
M C
MC
Bluestone
J A
JA
Miller
S D
SD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018122:B7-1 Antigen / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000503:physiopathology*; D000939:Epitopes / Q000187:drug effects*; D005260:Female; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D012008:Recurrence; D012074:Remission Induction
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments