No abstract

Amounts of trehalose-6,6-dimycolate as small as 1 to 5 ,ug can, after intravenous injection, induce in the lungs of mice formation of tubercles in which the cellular composition is indistinguishable from that in tubercles formed after an infection with living BCG bacilli. The strongest cellular response in mice was induced by cord factor from Mycobacteriwn kansasii; the weakest was induced by cord factor from the BCG strain of M. bovis. It was found that three intravenous injections of cord factor induced a more extensive cellular response than did one injection of the same total amount of cord factor. Mice treated intravenously with cord factor were protected against an intravenous challenge with the virulent H37Rv strain of M. tuberculosis. The cellular response in the lungs of mice to intraperitoneal injections of living BCG and cord factor was very weak compared with that after intravenous injections. Intraperitoneal vaccination of mice with cord factor did not protect the mice against a challenge with virulent tubercle bacilli. Mice vaccinated intraperitoneally with BCG were immunized although no granulomas, or very few, were present in the lungs at the time of the challenge. The significance of the cellular response induced by cord factor is discussed.

Trehalose-6,6-dimycolate (cord factor), a glycolipid from mycobacteria, suppressed the development of urethan-induced tumors in the lungs of mice to a similar degree as living Mycobacterium bovis (strain BCG) bacilli. The inhibition was apparently due to the host cellular reaction caused locally by cord factor.

Ten micrograms of trehalose-6, 6′-dimycolate (cord factor), injected into the footpad of mice, induced histological changes similar to those following injection of living BCG bacilli. Both materials induced in the draining lymph nodes the formation of granulomas composed of epitheloid cells, macrophages, and small numbers of lymphocytes. Apart from the granulomatous inflammatory process, marked hyperplasia of the lymphoid tissue in the paracortical zone of the nodes and accumulations of macrophages were evident. In some cases, the macrophages were very numerous and replaced part of the lymphoid tissue. Compared to cord factor, wax D showed weak granulomagenic activity. Only slight and transient inflammation was found in the footpads as well as transient slight lymphoid hyperplasia. Wax D also induced small accumulations of macrophages. Complete Freund's adjuvant induced, under the same experimental conditions, large accumulations of macrophages in the draining lymphnode and lymphoid hyperplasia in the paracortical zone. No cellular reaction was seen in the liver, spleen, and lungs after injection of cord factor and BCG into the footpads of the animals. The results and implications are discussed.