Russell S. Weiser

Homograft target cells, specific destruction in vitro by contact interaction with immune macrophages.

Specific adherence and mutual immunologic destruction occurred after contact in vitro of immune peritoneal macrophages from C57BI/6K mice with homograft target cells from A/Jax mice. Cell destruction apparently resulted from a nonphagocytic mechanism involving cell contact rather than humoral antibody. Cell destruction was determined by a plaque technique with either immunecells or target cells as monolayers.

The β-glucosaminidase activity of egg-white lysozyme☆

Abstract Substances of natural and synthetic origin were used to determine the chemical linkages attacked by crystalline egg-white lysozyme. Whereas, lysozyme was observed to possess β-glucosaminidase activity, as indicated by its capacity to hydrolyze chitin, a known β-glucosaminide bonded by i , 4 linkages, it failed to hydrolyze either the α or the β form of synthetic phenyl-N-acetylglucosaminide.

Homograft target cells: contact destruction in vitro by immune macrophages.

Specific adherence of immune macrophages to monolayers of target cells is a passive phenomenon which represents only the first step in the mutually destructive interaction of immune macrophages and target cells. A specific hemagglutinin, responsible for specific adherence, was eluted from well-washed immune macrophages by heat treatment. The nature of the events in the interaction subsequent to adherence are unknown, but apparently demand the biosynthetic activities of the immune macrophage.

MECHANISMS OF TUMOR HOMOGRAFT REJECTION: THE BEHAVIOR OF SARCOMA I ASCITES TUMOR IN THE A/JAX AND THE C57BL/6K MOUSE*

The respective roles that classical humoral antibodies and hypothetical “cellassociated” antibodies may play in tumor homograft rejection and the mechanisms by which they act remain major unsolved problems in homograft immunity. Whereas classical humoral antibodies to tumor homografts are commonly produced, their participation in tumor rejection has been clearly demonstrated only in a limited number of tumor-host combinations. Tumors derived from cells of the lymphoid series appear to be particularly susceptible to in vivo destruction by humoral antibody. Excellent discussions of the evidence bearing on the problem of the mechanisms of tumor homograft rejection have been presented recently by Gorer,’ Amos: and Snell and co-~orkers .~ The purpose of the present investigation is to gain further information about the mechanisms by which cell-associated antibody factor of immune host cells may accomplish the destruction of tumor cell homografts. The system, Sarcoma I (Sa I) in the C57BL/6K mouse, was chosen because it is one in which homograft rejection appears to depend solely on cell-associated antibody. Indeed, in this system classical humoral antibody exerts a suppressive rather than an augmentative effect on tumor rejection and induces an “immunological enhancement” of tumor growth rather than i m m ~ n i t y . ~ Sarcoma I originated in 1947 in a mouse of the Strong A strain that had been treated with dibenzanthracene. The tumor grows progressively in the A/ Jax subline of the Strong A mouse and kills 100 per cent of the animals. In contrast, mice of the resistant C57BL/6K strain, given a standard dose of 30 million ascites tumor cells by the intraperitoneal route, reject the tumor in essentially 100 per cent of the cases. The tumor shows unrestricted growth in the animals until the 6th or 7th day, when rejection begins. Rejection is largely completed by the 8th day, and the animals remain immune to rechallenge for weeks thereafter. Since our preliminary attempts failed to demonstrate that Sa I cells are destroyed by reaction in vitru with immune cells, attention was centered on in vizw studies of interaction between immune host cells and tumor cells. If the rejection of Sa I by the C57BL/6K mouse results from contact of immune

A Bacteriophage for Mycobacterium smegmatis.

Summary A bacteriophage speciric for M. smegmatis was isolated from sarnples of compost and soil by specific enrichment with a heavy washed suspension of M. smegmatis. The method of enrichment employed may be useful in the isolation of other phages.

The Tuberculin Reaction. I. Passive Transfer of Tuberculin Sensitivity with Cells of Tuberculous Guinea Pigs.

Summary Homologous passive transfer of tuberculin sensitivity was accomplished with the peritoneal and splenic cells of guinea pigs infected with the B.C.G. strain of Mycobacterium tuberculosis. The possible mechanism and factors involved in passive transfer of tuberculin sensitivity are discussed.

Tuberculin Reaction. III. Transfer of Systemic Tuberculin Sensitivity with Cells of Tuberculous Guinea Pigs.

Summary The results of the present investigations establish tlhat systemic tuberculin sensitivity can be passively transferred in the guinea pig with the cells of induced peritoneal exudates of tuberculous donors. The systemic shock produced in recipients passively sensitized in this manner is of the typical delayed tuberculin type. These findings supplement the observation of Chase1 that cutaneous tuberculin sensitivity can be passively transferred in the guinea pig with the cells of induced peritoneal exudates of donors sensitized with heat-killed tubercle bacilli by providing additional evidence that the sensitivity transferred is of the tuberculin type. In a limited number of trials it was also found that desensitization of tuberculous donors with tuberculin tends to abolish the capacity of their peritoneal cells to passively transfer tuberculin sensitivity. If this observation is confirmed it will provide strong evidence that desensitization results from the saturation of fixed cellular antibody with antigen.

Anaphylaxis in the mouse produced with soluble complexes of antigen and antibody.

Summary 1) Soluble BSA anti-BSA complexes formed in regions of extreme antigen excess are less anaphylactigenic for the mouse than similar complexes formed in regions of low antigen excess. 2) The hypothesis is advanced that anaphylactigenic activity of these complexes for the mouse is dependent upon their capacity to react with complement.

Tuberculin Reaction. II. Cytotoxicity of Tuberculin for Splenic Explants of Desensitized Tuberculous Guinea Pigs.

Summary Experiments are presented which show that the in vitro effects of tuberculin in suppressing the initial migration of leucocytes from splenic explants of tuberculous guinea pigs is markedly reduced by specific desensitization. This finding indicates that the cytotoxic effect of tuberculin on tissue explants of tuberculin-sensitive animals is the result of the interaction of a sessile antibody with specific antigen.

THE PATHOGENESIS OF ACUTE ALLOGENEIC DISEASE IN MICE STUDIED BY PARABIOSIS.

Mice of the A/Jax and C57BL/Ks strains were joined in parabiosis by coeleo-anastomosis and “vascular-anastomosis” in all combinations. One parabiont of each pair was injected i.p. with allogeneic immune peritoneal cells from C57BL/Ks animals. Attempts were made to detect the release of antibody from immune cells transferred to normal A/Jax and to normal C57BL/Ks animals. The observations which indicate that acute allogeneic disease (AAD) results from cell-associated immunity and that death is due to circulatory effects rather than a systemic toxin are: (a) humoral antibodies were not detected in C57BL/Ks or A/Jax recipients of immune cells; (b) in A/Jax-C57BL/Ks parabionts with established cross-circulations, but without coeleo-anastomosis, AAD was restricted to A/Jax animals and only developed when the cells were injected into the A/Jax partner. The C57BL/Ks animals showed simple fluid loss to the A/Jax partners; (c) in A/Jax-C57BL/Ks parabionts with coeleo-anastomosis, but without established cross-circulations, the A/Jax animal died and the C57BL/Ks animal was spared regardless of which partner was injected. Although cell-free extracts from 4 to 6 × 109 immune peritoneal cells caused toxemia and death of mice, the effect was nonspecific and pathology typical of AAD was not present.