CYTOKINE MESSENGER-RNA EXPRESSED IN TUBERCULIN SKIN-TEST BIOPSIES FROM BCG-VACCINATED AND MYCOBACTERIUM-BOVIS INOCULATED CATTLE

To obtain a better understanding of the delayed-type hypersensitivity reaction to Mycobacterium bovis, we measured the expression of cytokin e mRNA from tuberculin skin test biopsies of cattle. Nonvaccinated and BCG-vaccinated cattle were inoculated intratracheally with a low dose of virulent M. bovis or sham-inoculated and 20 weeks later were skin tested with tuberculin. At necropsy 1-2 weeks later, tuberculous lesio ns were found in six of the nine non-vaccinated and three of the nine BCG-vaccinated animals. All of the lesioned and the majority of the no n-lesioned M. bovis inoculated cattle showed a distinct skin swelling response to tuberculin, irrespective of vaccination. However, cattle w ith tuberculous lesions displayed larger skin swelling responses than non-lesioned cattle. Tuberculin-induced expression of IFN-gamma, IL2, IL4, IL10 and TNF-alpha mRNA occurred in the skin biopsies of all of t he lesioned, M. bovis inoculated animals except for an absence of tube rculin-induced TNF-alpha mRNA expression in two animals. A lower propo rtion of the non-lesioned M. bovis inoculated cattle displayed tubercu lin-induced expression of the five cytokine mRNA. There was no evidenc e of a unique pattern of cytokine expression which could be used to di stinguish between diseased and protected animals. By 28 weeks after va ccination, the three BCG-vaccinated, sham-inoculated cattle displayed minimal skin swelling response to tuberculin, but tuberculin-induced e xpression of IFN-gamma, IL2, IL4, IL10 and TNF-alpha mRNA was observed in skin biopsies of all of these animals. The pattern of cytokine mRN A expressed in the tuberculin skin test reaction site of cattle appear ed to be typical of a mixed T helper O-like cell phenotype response an d there was no clear-cut relationship between the size of the tubercul in skin swelling response and cytokine mRNA expression.