Inhibition of Tuberculin Skin Hypersensitivity in Guinea Pigs by Injection of Tuberculin and Intact Tubercle Bacilli during Fetal Life

FEMALE GUINEA PIGS WERE SUBJECTED TO LAPAROTOMY AT DIFFERENT STAGES OF PREGNANCY, AND THEIR FETUSES INJECTED THROUGH THE UTERINE WALLS WITH ONE OF THE FOLLOWING PREPARATIONS: Old Tuberculin, tubercle bacilli of the BCG strain killed by heat or exposure to phenol, and living BCG. A large number of the animals injected in utero with Old Tuberculin failed to develop skin hypersensitivity to P.P.D. following vaccination with 200 or 800 gamma phenol-killed tubercle bacilli (BCG) in early adulthood. Normal control animals were sensitized by vaccination with such quantities of phenolized BCG. The failure of animals which had been injected with Old Tuberculin in fetal life to respond hypersensitively to P.P.D. after adult vaccination with tubercle bacilli is ascribed to their acquisition of a state of immunological tolerance to tuberculoprotein (tuberculin tolerance). Fetal injection with killed BCG conferred a state of tolerance on a few of the animals, and rendered others tuberculin-sensitive. Fetal injection with living BCG sensitized most of the animals to tuberculin, even when fetal exposure was as early as 46 days before birth, and induced tolerance in none. Fetuses of the same litter, injected simultaneously with identical inocula, often responded differently, some becoming tolerant to tuberculin, others developing hypersensitivity, and still others remaining immunologically unaffected, becoming neither sensitive nor tolerant. The state of tuberculin tolerance induced in these experiments was limited. When tolerant animals were revaccinated with living BCG several weeks after vaccination with phenol-killed bacilli, they developed as high a degree of tuberculin skin sensitivity as the originally non-tolerant animals.