Anti-CD43 monoclonal antibody L11 blocks migration of T cells to inflamed pancreatic islets and prevents development of diabetes in nonobese diabetic mice.
Nonobese diabetic mice are a well-known model for human insulin-dependent diabetes mellitus. These mice develop autoimmune-mediated inflammation of the pancreatic islets, followed by destruction of the insulin-producing beta cells and development of diabetes. Nonobese diabetic mice also have salivary gland inflammation, and serve as a model for human Sjogren's syndrome. T cells are a prominent component of the inflammatory infiltrate in these sites, and T cell recruitment from the blood is thought to be essential for the initiation and maintenance of pathologic tissue damage. A unique mAb to murine CD43, L11, has recently been shown to block the migration of T cells from blood into organized lymphoid tissues. Here we demonstrate that L11 significantly inhibits T cell migration from blood into inflamed islets and salivary glands. Treatment of nonobese diabetic mice with L11 from 1 to 4 or 8 to 12 wk of age led to significant protection against the development of diabetes. Moreover, protection was long-lived, with decreased incidence of diabetes even months after cessation of Ab administration. When treatment was started at 1 wk of age, L11 inhibited the development of inflammation in pancreatic islets and salivary glands. L11 treatment had no long-term effect on numbers or phenotypes of peripheral lymphocytes. These data indicate that anti-CD43 Abs that block T cell migration may be useful agents for the prevention or treatment of autoimmune diseases including insulin-dependent diabetes mellitus and Sjogren's syndrome.
Johnson
G G
GG
Department of Pathology, Stanford University School of Medicine, CA 94305, USA.
Mikulowska
A
A
Butcher
E C
EC
McEvoy
L M
LM
Michie
S A
SA
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D015703:Antigens, CD; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D007116:Immunization, Passive; D016130:Immunophenotyping; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology*; D007765:Lacrimal Apparatus / Q000276:immunology / Q000473:pathology; D051917:Leukosialin; D018655:Lymphocyte Count; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D012469:Salivary Glands / Q000276:immunology / Q000473:pathology; D012795:Sialoglycoproteins / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051917:Leukosialin; D012795:Sialoglycoproteins; C497863:Spn protein, mouse