Prevention of graft rejection in allogeneic bone marrow transplantation: I. Preclinical studies with antithymocyte globulins.
Heterologous horse antithymocyte globulins (ATG) were investigated in vitro as potential immunotherapeutic reagents in the prevention of bone marrow graft rejection by allogeneic recipients. Different lots and concentrations of ATG were evaluated for their ability to inactivate natural killer (NK) cells, IL-2 cultured 'augmented' NK cells, and/or cytotoxic T cells (CTL) using the 51Cr-release assay for measurement of cytotoxic activity. In vitro incubation of peripheral blood mononuclear cells (PBMC) with a prototype non-myelotoxic ATG (ATGP12) at 0.1 mg/ml (a concentration which can be achieved with an i.v. infusion of approximately 30 mg ATG/kg daily) variously inhibited NK activity (0-100%); whereas treatment with the same concentration of ATGP12 and autologous human complement completely inhibited NK, as well as 'augmented' NK function from all normal individuals tested. Incubation of T cytotoxic effector cells with ATGP12 alone also significantly abrogated primed T cell cytotoxicity. These studies demonstrate that lots of ATG can be easily prescreened and titered in vitro in order to identify immunosuppressive reagents capable of inhibiting the MHC restricted and non-restricted cytotoxic cells, which can survive chemotherapy and radiation, and may play a critical role in resistance to engraftment of T cell-depleted marrow.
Malilay
G P
GP
Department of Pediatrics, University of Minnesota, Minneapolis.
Sevenich
E A
EA
Condie
R M
RM
Filipovich
A H
AH
D000961:Antilymphocyte Serum; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000494:pharmacology*; D003601:Cytotoxicity Tests, Immunologic; D006084:Graft Rejection; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008212:Lymphocyte Depletion; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000961:Antilymphocyte Serum; D007376:Interleukin-2; D003165:Complement System Proteins