Evidence that anti-LFA-1 in vivo improves engraftment and survival after allogeneic bone marrow transplantation.
The LFA-1 molecule is a member of the leukocyte adhesion complex (CD11/CD18) that is critical to adhesion and effector function of T cells and NK cells. Both T cells and NK cells play important roles in bone marrow graft rejection, and anti-LFA-1 MAbs inhibit in vitro T cell and NK cell cytotoxicity. We here describe the in vivo use of a monoclonal antibody to the alpha chain of LFA-1 (CD11a) to prevent rejection of T cell-depleted allogeneic bone marrow. Animals receiving anti-LFA-1 and 1100 cGy total-body irradiation showed improved hemopoietic and immunologic reconstitution one month after BMT when compared with animals receiving TBI alone. Animals in the anti-LFA-1 group showed significantly improved long-term survival, and had no deficits in long-term lymphohemopoietic reconstitution.
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
P J
PJ
van Dijken
T
T
Ghayur
P
P
Mauch
J
J
Down
S J
SJ
Burakoff
J L
JL
Ferrara
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000943:Antigens, Differentiation / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002469:Cell Separation; D006085:Graft Survival; D006410:Hematopoiesis; D007109:Immunity; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D008815:Mice, Inbred Strains; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D016169:Lymphocyte Function-Associated Antigen-1; D016028:Receptors, Leukocyte-Adhesion