Assessment of tolerance induction to cardiac allograft by anti-ICAM-1 and anti-LFA-1 monoclonal antibodies.
BACKGROUND
Transplantation tolerance is induced by selective manipulation of intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1) molecules in the adult mouse. However, the mechanism of this tolerance induction has not been elucidated.


RESULTS
C3H/He mice were heterotopically transplanted with BALB/c hearts; recipients were injected with anti-ICAM-1 and anti-LFA-1 monoclonal antibodies (mAbs). Of 3-day administration of both mAbs at 50 micrograms/day, all recipients accepted cardiac allografts indefinitely (n = 20); this also occurred in 5 of 10 mice that were not treated until day +4 or day +5. Long-term cardiac allograft acceptance was also achieved in thymectomized recipients. This tolerance could not be abrogated by the injection of either naive recipient lymphocytes or sensitized lymphocytes taken from the recipient strain mice that rejected the same donor strain hearts. Mixed lymphocyte culture showed that splenocytes from allograft recipient mice treated with the mAbs showed normal allogeneic response without donor alloantigen specificity.


CONCLUSIONS
These results demonstrate the unique character of the peripheral tolerance induced by anti-ICAM-1 and anti-LFA-1 mAbs. Further studies are required to elucidate detailed mechanisms of transplantation tolerance development.
Isobe
M
M
First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Suzuki
J
J
Yamazaki
S
S
Horie
S
S
Okubo
Y
Y
Sekiguchi
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016027:Heart Transplantation / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1