Inhibition of canine NK activity by anti-CD18 monoclonal antibody, UV irradiation and cyclosporine.
Previous studies from our laboratory have shown that large granular lymphocytes (LGL) mediate natural killer cell (NK) activity in dogs and that host LGL are associated with graft failure in a canine model of histoincompatible marrow transplantation. We now report studies on the effects of anti-CD18 monoclonal antibody (MAB) 60.3, ultraviolet (UV) irradiation and cyclosporine (CSP) on in vitro canine NK function. Treatment with the murine anti-CD18 MAB 60.3 produced marked diminution in lytic function (mean 79% inhibition). UV irradiation at doses greater than 1.6 millijoules/cm2 completely eliminated NK function; this effect was not due to defective effector/target conjugate formation. CSP also inhibited NK function, although in vitro lytic activity was not completely blocked (mean of 44% inhibition) at concentrations which correspond to those achieved in vivo (400 ng/mL). These observations form a basis for future investigations aimed at preventing graft failure in the canine model of histoincompatible marrow transplantation by blocking NK function in vivo.
Loughran
T P
TP
Fred Hutchinson Cancer Research Center, Seattle, WA.
Deeg
H J
HJ
Storb
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology*; D018821:CD18 Antigens; D016572:Cyclosporine / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000502:physiology* / Q000528:radiation effects*; D014466:Ultraviolet Rays
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D016572:Cyclosporine