Anti-LFA-1 (CD11a) monoclonal antibody interferes with neonatal induction of tolerance to alloantigens.
The injection of (C57BL/6 x BALB/c)F1 spleen cells into newborn BALB/c mice results in the induction of a specific cytotoxic T lymphocyte (CTL) tolerance to the alloantigens. On the contrary, alloreactive CD4+ T cells persist in the host and are still able to activate autoreactive F1 B cells to produce autoantibodies. This state of "split tolerance" is closely associated with the development of a lupus-like autoimmune syndrome. The LFA-1 integrin plays a relevant role in homing, intercellular adhesion and tranduction of co-stimulatory signals in leukocytes. Because of the beneficial effects of anti-LFA-1 monoclonal antibodies (mAb) treatment in various models of organ transplantation and autoimmune disease, we have investigated if such a treatment could interfere with the induction of neonatal tolerance or the development of the autoimmune syndrome in F1 cell-injected newborn mice. For this purpose, BALB/c mice neonatally injected with F1 cells were treated from day 1 up to day 15 with a non-cytotoxic anti-LFA-1 (CD11a) mAb. Anti-LFA-1 mAb treatment interfered with the persistence of a stable chimerism and with the establishment of CTL tolerance, as shown by rejection of allogeneic skin grafts and F1 B cells, and by a normal in vitro CTL activity against the corresponding alloantigens. As a consequence, these mice did not develop the characteristic autoimmune features seen in close association with an effective induction of CTL tolerance to alloantigens. These results stress the importance of the interactions between LFA-1 and its ligands during the neonatal induction of tolerance to alloantigens.
Schurmans
S
S
WHO Immunology Research and Training Center, Department of Pathology, CMU, University of Geneva.
Gonzalez
A
A
Revilla
C
C
Ramos
A
A
Lambert
P H
PH
Merino
J
J
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000502:physiology*; D018845:CD11 Antigens; D007108:Immune Tolerance; D007519:Isoantigens / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D007519:Isoantigens; D016169:Lymphocyte Function-Associated Antigen-1