The role of delayed hypersensitivity in the enhancement of host resistance to infection.

Swiss-Webster mice were vaccinated by the intraperitoneal route (i.p.) with Mycobacterium tuberculosis BCG and challenged i.p. 4-10 weeks later with 10(4) virulent Salmonella typhimurium in the presence or absence of purified derivative (PPD) of tuberculin. Normal control mice were similarly challenged. Such an infection was fatal to the normal mice within 12 days. BCG vaccination prolonged the survival time and protected about 36% of the salmonella-infected mice from death. In contrast, tuberculin sensitivity, elicited in the BCG-vaccinated mice, significantly increased the survival time and protected about 70% of the mice against an otherwise fatal challenge. When these experiments were repeated using an infective dose of 10(6) organisms, the protective effect of the tuberculin reaction became substantially reduced, but there remained a statistically significant improvement in the survival distribution of the challenged mice as compared with that among the BCG-vaccinated mice. The examination of peritoneal washings obtained from BCG-vaccinated mice stimulated with PPD showed that the enhanced resistance to salmonella infection was directly associated with a quantitatively increased influx of phagocytic leukocytes accumulating at the site of infection as a result of the elicitation of tuberculin sensitivity.