Lymphocyte function associated antigen-1, integrin alpha 4, and L-selectin mediate T-cell homing to the pancreas in the model of adoptive transfer of diabetes in NOD mice.
The involvement of adhesion molecule in the process of T-cell homing to the pancreas was investigated in the model of the T-cell transfer of type I diabetes in NOD mice. Treatment of mice using monoclonal anti-lymphocyte function associated antigen (LFA)-1, anti-integrin alpha 4, anti-intercellular adhesion molecule (ICAM)-1, and anti-L-selectin antibodies (monoclonal antibodies [mAbs]) gave rise to a partial or complete prevention of diabetes via different mechanisms of protection. On day 20 posttransfer, diabetes was only observed in control mice (26 of 32) and in few mice treated with the anti-L-selectin mAbs (3 of 24). On day 60, the best protection was observed using the anti-LFA-1 or the anti-integrin alpha 4 mAbs with 3 of 11 and 2 of 5 diabetic mice, respectively. On day 20, no insulitis was observed in the pancreases of mice treated with these mAbs compared with the pancreases of controls, suggesting that such treatment blocked the penetration of T-cells into the islets. In vitro adhesion assays confirmed that adhesion of T-cells to the pancreatic endothelium was blocked, except when using the anti-L-selectin mAb, which induced a modification of the traffic of the transferred T-cells; the ability of T-cells to migrate into the pancreatic lymph nodes was significantly reduced (10.4 vs. 22%). Anti-LFA-1 mAbs did not modify such T-cell trafficking. The present study, therefore, elucidates the role of LFA-1, integrin alpha 4, and L-selectin in T-cell homing to the pancreas, first step of the cascade of events leading to type I diabetes.
Fabien
N
N
Institute National de la Sante et de la Recherche Medicale 197, Faculty of Medecine Alexis Carrel, Lyon, France.
Bergerot
I
I
Orgiazzi
J
J
Thivolet
C
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D002448:Cell Adhesion; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D039441:Integrin alpha4; D019041:L-Selectin / Q000276:immunology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018448:Models, Immunological; D010179:Pancreas / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016169:Lymphocyte Function-Associated Antigen-1; D019041:L-Selectin; D039441:Integrin alpha4