[Effect of neurolysis on agglutinogenesis].
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Immune serums prepared in rabbits with antigens made from normal mouse organs and tissues that were presumably devoid of large numbers of lymphocytic cells (notably kidney, liver, brain, whole embryos, and erythrocytes) proved lethal for the cells of several transplanted mouse lymphomas in vitro in the presence of complement; but these immune serums, when given intraperitoneally in large amounts to susceptible mice that had been implanted subcutaneously with lymphoma cells of one or another of several types, failed entirely to inhibit growth of the lymphoma cells in vivo. In contrast, immune serums made with cells procured from transplanted mouse lymphomas as antigens, and those made with cells from normal mouse thymus or lymph nodes, acted even more powerfully upon the several types of lymphoma cells in vitro than did the immune serums prepared with normal mouse organs, and when given intraperitoneally to implanted mice they brought about death of the lymphoma cells in vivo, the effect being to a considerable extent specific and referable to an antibody that reacts with neoplastic and non-neoplastic lymphocytic cells of mice, as absorption experiments disclosed. In comparative tests, furthermore, the anti-lymphoma serums acted more powerfully upon the lymphoma cells in vivo than did such chemotherapeutic agents as amethopterin, azaguanine, ethionine, azaserine, and 6-mercaptopurine, given singly or in various combinations in maximal tolerated amounts, though their effects were not so powerful as those exerted by normal guinea pig serum on lymphoma cells of two types that are susceptible to its action in vivo. The significance of the findings was briefly discussed.
In earlier studies it was shown that if rabbit lymph node cells were incubated with Shigella-trypsin filtrate and transferred to other, recipient, rabbits, agglutinins to Shigella appeared subsequently in the sera of the recipients. However, if leucocytes from the donor rabbits were injected into the recipients at a suitable interval prior to lymph node cell transfer, agglutinins to Shigella did not appear after cell transfer. In the present study, a number of experiments were done which bear on the immunologic character of this suppressive effect on the transferred cells, the "pre-injection effect." X-irradiation of the recipients before the injection of donor leucocytes led to a decrease in the extent of the pre-injection effect, i.e. to the appearance of higher agglutinin liters, in the recipient animals. It was found possible to transfer the pre-injection effect by cells of rabbit lymph nodes draining sites of injection of rabbit leucocytes. No such effect was obtained with heated aliquots of these cell suspensions or with lymph node cells from sheep-erythrocyte-injected donors. It was also possible to transfer the pre-injection effect passively by serum. Suppression of transferred lymph node cells was observed regularly after injection of serum pooled from groups of rabbits which had been injected with leucocytes pooled from the blood of 60 to 70 rabbits. The active material in anti-leucocyte serum could be precipitated in the globulin fraction of the serum and could be removed by absorption with rabbit lymph node cells. In the course of experiments on the passive transfer of the pre-injection effect by antisera of individual rabbits to leucocytes of individual donor rabbits, evidence was obtained of the existence in the sera of some normal rabbits of antibodies to some of the rabbit leucocyte antigens.
Renal glomerular lesions were induced by rabbit serum containing antibody to rat collagen injected intravenously into rats prepared with subcutaneously administered Freund adjuvant. Neither the anti-collagen serum nor the adjuvant alone induced the lesion. The lesions were characterized by diffuse glomerular injury with swelling, shredding, and fusion of the basement membranes, crescent formation, cellular proliferation, numerous multinuclear giant cells, and capillary hyaline thrombi. Various rabbit antisera, including those against fish collagen or rat serum failed to induce the renal lesion when substituted for anti-rat collagen serum. Also, anti-rat collagen serum absorbed with its homologous antigen, native rat collagen, failed to induce the lesion. Although complete adjuvant, i.e. with mycobacteria, in which normal serum was incorporated enhanced the glomerular lesion which resulted from intravenous injection of anti-collagen serum, the incomplete adjuvant without serum was sufficient. Comparison of the renal lesions induced by anti-collagen serum with nephrotoxic nephritis induced in rats by rabbit anti-kidney serum showed that they differ histologically. Also the antisera used to produce these two renal lesions differ immunologically. Antibodies to normal rabbit serum developed in rats injected intravenously with rabbit anti-rat collagen serum after preparation with adjuvant, but not when adjuvant was omitted. The pathogenesis of the renal injury is discussed as a manifestation of an antigen-antibody reaction, with nephritis occurring only after the adjuvant-stimulated antibody to the rabbit globulin has been formed in the rat and has reacted with the rabbit anti-rat collagen already fixed by its homologous antigen in the kidney.
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