Development of teratocarcinoma does not impair immunization of mice against Listeria monocytogenes. Endotoxin injection a short time before tumor cell inoculation allows the growth of teratocarcinoma in non syngenic mice despite immune stimulation. In contrast with this absence of impaired systematic immunity, teratocarcinoma cells were found to repulse macrophages in vitro. This effect on macrophages was also found with three other malignant cells and with trophoblast cells. In vivo, teratocarcinoma cells were found to impair local inflammation. These cells and other malignant cells are able to produce a compound(s) of molecular weight between 103 and 104, which prevents inflammatory reaction. These results suggest that mouse teratocarcinomas and other tumors by-pass the host immunological system of surveillance by at least two mechanisms: a direct toxic effect on macrophages and the release of an inhibitor of inflammation. The possible relations between these properties of malignant cells and physiological functions of trophoblast are discussed.Like many tumors, mouse teratocarcinomas can be transplanted and grown in syngenic adult mice (1), although they possess a surface antigen considered "foreign" by these animals (2). In this paper, we report the results of experiments designed to analyze the mechanism allowing teratocarcinoma cells to by-pass the host immunological system of surveillance. This mechanism appears to operate at least at two levels, i.e., diapedesis and macrophage-tumor cell interaction. The role of cellular immunity in host resistance against tumor is well established (6). In order to determine whether or not the growth of teratocarcinoma results in a systemic decrease in cellular immunity, we have followed the capacity of mice, harboring such tumors, to be immunized against Listeria monocytogenes. This immunity is known to depend on the activation of macrophages by sensitized T lymphocytes (thymus-derived lymphocytes) (7). The results of such an experiment are reported in Table 1

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The susceptibility of mice to experimental infection with Corynebacterium kutscheri was studied by comparing the host response to this organism of mice obtained from 31 different colonies, representing 15 different genetic types. A standardized infective dose, administered intravenously, made it possible to separate the animals into two sharply differentiated groups. All the animals of the following colonies died: Swiss Lynch, Swiss R/J, A/Jax, Princeton, RFVL, and CF1 (SPF). All the animals of the following colonies survived: CFW, ICR, Balb/C, BSVS, BRVR, RIII, YBR/He, DBA/2 (from 3 different colonies), and C57B1/6 (from 12 different colonies). The two highly inbred strains, Swiss Lynch and C57Bl/6, were selected as prototypes of susceptible and resistant animals respectively, for more detailed studies. Following injection of an infective dose of 0.2 x 10–4 ml of culture of C. kutscheri, all Swiss Lynch animals died within 3 to 11 days (the majority within 4 to 7 days); whereas all C57Bl/6 animals survived. The outcome of the infection in each strain was independent of age and sex of the animals. In Swiss Lynch animals, the corynebacteria multiplied rapidly in lungs, liver, kidneys, and to some extent in the spleen. In C57Bl/6 mice, there was no increase of the corynebacterial population in the lungs, liver, or spleen, but multiplication occurred in the kidneys during the early phase of the infectious process with resultant abscess formation. However, the renal infection soon subsided leaving no residual pathology. C. kutscheri could not be recovered from any organs of C57Bl/6 mice sacrificed 16 days after infection. Homogenates of organs from Swiss Lynch mice obtained while the infection was progressing contained only typical C. kutscheri. In contrast, the lungs and livers of similarly infected C57Bl/6 animals occasionally yielded large numbers of small translucent colonies distinctly different from those of typical corynebacteria. The use of mouse strains differing markedly in response to experimental infection with C. kutscheri is presented as a biologic model lending itself to further studies concerning factors which condition resistance to corynebacterial pseudotuberculosis, a disease of practical importance for investigators conducting experiments with murine species.

Latent corynebactenai infection occurs naturally in many strains of mice. It can be evoked into the active disease, pseudotuberculosis, by a single injection of 10 mg of cortisone. The cortisone effect was tested in 21 colonies, representing 11 genetically different strains of mice. Animals of the C57B1/6, DBA/2, and RIII strains were shown to be latently infected with Corynebacterium kutscheri by the fact that they developed fatal pseudotuberculosis following cortisone treatment. Virulent C. kutscheri could not be isolated from homogenates of organs obtained from latently infected animals before cortisone administration; however, these homogenates yielded small translucent colonies of avirulent organisms. Recovery of these atypical colonies was facilitated by preincubating the organ homogenates before plating. The organisms constituting such colonies differed morphologically and immunologically from C. kutscheri, but had similar biochemical properties with the exception that they lacked urease and catalase activity. Mice treated with cortisone yielded both the avirulent bacteria and virulent C. kutscheri. The latter was the predominant organism present in the organs at the height of infection. Injection of avirulent organisms into Swiss Lynch mice, which are normally free of latent corynebacteria, occasionally established a latent infection which could be converted into corynebacterial pseudotuberculosis by cortisone. Cultures of fully virulent C. kutscheri were then obtained from the lesions. Latency was produced experimentally with a streptomycin-resistant strain of virulent C. kutscheri (CKsr) derived from the stock culture. When sublethal doses of CKsr were injected into NCS mice (Institut Pasteur colony), they induced a latent infection characterized by the presence of avirulent organisms possessing the streptomycin resistance marker. These were isolated in the form of small translucent colonies from the livers of the infected animals. Administration of cortisone to these animals subsequently evoked active infection from which virulent CKsr could be obtained. Injection of the avirulent streptomycin-resistant organisms into normal NCS mice established a latent infection which could be uniformly converted into corynebacterial pseudotuberculosis by cortisone. The virulent C. kutscheri obtained from the lesions bore the genetic marker of streptomycin resistance, thus being identical with CKsr. Except for streptomycin resistance, the avirulent organisms isolated from the experimentally induced latent infections were identical with those found in the naturally occurring latent infections. These results suggest that C. kutscheri can persist in vitro in an avirulent form which is resistant to the defense mechanisms of the host, and can thus establish a latent infection. Treatment of the animal with cortisone results in the conversion of the avirulent form into virulent C. kutscheri, and of the latent infection into active corynebacterial pseudotuberculosis. The findings are discussed with regard to their relevance to infection immunity, and to the conversion of latent infection into overt disease.

Injection of bacterial phospholipid extracts (EBP) into mice increased their resistance towards a Listeria monocytogenes infection. The blood clearance of virulent Salmonella typhimurium was enhanced and the degree of clearance correlated with the dose of extract injected. The multiplication of Listeria monocytogenes in spleen and liver of mice was inhibited and this inhibition was also correlated with the amount of extract injected. The absence of apparent toxicity in mice, of splenoand hepatomegaly, and of lymphoid hyperplasia, distinguish this immunostimulant from other known bacterial stimulants of host resistance to infection.