Cell-mediated immunity in canine marrow graft recipients given cyclophosphamide

The cellular immune status of 48 canine chimeras was studied between 15 days and 3 years after a lethal dose of cyclophosphamide (CY) and an allogeneic marrow graft. Marrow graft recipients were given no further immuno-suppressive treatment. Recovery of total white blood cell counts was complete by day 20 after grafting. Peripheral blood lymphocyte counts did not reach the normal range until day 100. Short-term chimeras (less than 100 days postgrafting) showed marked impairment of cell-mediated immunity as indicated by the inability to respond adequately to nonspecific mitogenic (PHA, ConA, PWM) and specific antigenic (allogeneic lymphocytes, PPD) stimulation in vitro. Skin test reactivity to PPD after immunization with BCG was also significantly depressed. Long-term chimeras (more than 100 days postgrafting) had normal in vitro response to mitogens; lymphocyte blastogenesis to specific antigens however remained decreased for prolonged periods postgrafting. The survival time at first set allogeneic skin grafts showed no significant difference between chimeras and normal control dogs. Lymphocyte transformation in response to stimulation with specific antigens may prove a useful parameter for the in vitro evaluation of defects in cellular immune reactivity following allogeneic marrow transplantation.