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Induction of Tuberculin Hypersensitivity and Serologic Unresponsiveness to Tubercle Bacilli in Newborn and Young Cuinea Pigs^1,2,

From the Basic Microbiology Research Laboaratory, Veterans Administration Hospital, Washington, D. C.

Abstract

The age at sensitization with tubercle bacilli was shown to have a marked influence on the expression of tuberculin skin reactivity in young guinea pigs. Animals varying in age from 0 to 4 weeks old were injected with 5 mg (dry weight) of heat-killed M. tuberculosis (H37Rv strain) and skin tested 2 weeks later with 5 µg of PPD. Only the 4-week-old animals exhibited tuberculin hypersensitivity to the same degree as similarly-sensitized adult animals. Evidence was provided to indicate that the failure of the younger animals to exhibit skin reactivity may reflect a nonspecific deficiency of the skin rather than a fault in functional immune capacity. The effect of varying the size of the sensitizing dose on tuberculin skin reactivity was not as striking as varying the age at sensitization. Positive skin reactions were noted following the use of sensitizing doses ranging from 0.125 mg to 5.0 mg when the animals were skin tested 2 weeks after injection. In contrast, the serologic reactivity of the sensitized young animals decreased as the sensitizing dose was increased above 0.5 mg. The 5-mg dose was found to induce serologic unresponsiveness quite effectively in newborn animals. Serologic unresponsiveness represented at least a 100-fold decrease in the circulating antibody response. It was suggested that serologic unresponsiveness may reflect a form of specific immune suppression. The implications of these findings to the use of acquired immunologic tolerance in guinea pigs as a model for study of the mechanisms of immunity in tuberculosis are discussed.

Footnotes

¹ Presented in part at the annual meeting of the American Association of Immunologists, April 18, 1967, in Chicago, Illinois.

² This work was supported in part by a research grant from the American Thoracic Society.