In vitro and in vivo immune response to specific antigens in canine marrow graft recipients.

Cellular and humoral immune reactivity to primary and secondary challenge with tetanus toxoid, diphtheria toxoid and keyhole limpet hemocyanin was studied in normal dogs and canine bone marrow chimeras prepared for marrow grafting by lethal doses of cyclophosphamide. Short-term chimeras (less than 100 days postgrafting) showed general impairment of immune function as indicated by marked depression of skin test reactivity, lymphocyte blastogenesis in vitro and antibody formation. Long-term chimeras (more than 100 days post-grafting) demonstrated gradual improvement of immunologic capacity related to the stage of postgrafting. Prolonged immunoincompetence was suggested by decreased lymphocyte proliferation in vitro in response to stimulation with tetanus and diphtheria toxoids and by incomplete conversion from 19S to 7S antibody synthesis. Lymphocyte blastogenesis to specific antigens may prove a useful parameter for the in vitro evaluation of defects in cell-mediated immunity following allogeneic bone marrow transplantation. Our findings of prolonged immunodeficiency in the preclinical canine model point out the necessity for vigilance in early detection and treatment of infection and underline the importance of approaches aimed at accelerating immunologic reconstitution.