Extracellular lysosome-associated membrane protein-1 (LAMP-1) mediates autoimmune disease progression in the NOD model of type 1 diabetes.
Treatment (from 5 to 25 weeks of age) with a novel blocking monoclonal antibody, mAb I-10, directed against the plasma membrane (pm) form of LAMP-1, protected against development of autoimmune diabetes in the NOD mouse. A shorter course of treatment, i.e. from 5 to 12 weeks of age, significantly reduced the occurrence of insulitis as well as disease onset. Interfering with pm-LAMP-1 required continuous treatment as tolerance was not observed when treatment was stopped, and no higher proportion of cells with a T regulatory phenotype (e.g. CD4(+)CD25(+)) were induced. The mechanism appears to involve modulating a proinflammatory cytokine, as the proportion of pancreatic-infiltrating IFN-gamma-positive cells was significantly reduced in the mAb I-10-treated group. These results demonstrate an unexpected role for pm-LAMP-1 in autoimmune disease progression, and suggest that further investigation should be performed to understand how this molecule modulates IFN-gamma-driven responses.
De Carvalho Bittencourt
Marcelo
M
Serono Pharmaceutical Research Institute, Geneva, Switzerland. marcelo.decarvalho@chu-fortefrance.fr
Herren
Suzanne
S
Graber
Pierre
P
Vilbois
Francis
F
Pasquali
Christian
C
Berney
Claude
C
Plitz
Thomas
T
Nicoletti
Ferdinando
F
Kosco-Vilbois
Marie H
MH
D000595:Amino Acid Sequence; D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology* / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology*; D015153:Blotting, Western; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D010179:Pancreas / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D007371:Interferon-gamma