Studies on the Immunological Response to Foreign Tumor Transplants in the Mouse

125

Regulatory effects of alloantigen-activated thymus-derived lymphocytes in mixed lymphocyte reactions have been demonstrated. Mice were injected into foot pads with allogeneic spleen cells; 4 days following sensitization spleen or regional lymph node cells from these animals were treated with mitomycin C and incorporated into MLR as regulator populations syngeneic to the responder cell type. Activated spleen cells suppressed MLR responses 60–90% whereas activated lymph node cells from the same animals enhanced MLR responses. Suppression by activated spleen cells was not due to cytotoxic effects nor to altered kinetics of the proliferative response. Studies of splenic suppressor cell generation in vivo revealed peak activity four days after alloantigen stimulation with no activity demonstrable at 7 days or at later times. Suppressor cell activity was abrogated by treatment with anti-θC3H serum and complement, and was not alloantigen specific.

Section: Resultsmentioning

confidence: 99%

Regulatory Mechanisms in Cell-Mediated Immune Responses

Rich

1974

125

“…The only differences found lay in the direction of prolonged survival of grafts in the serum-injected mice. Similarly, Mitchison (9)(10)(11) found that the transfer of serum from immunized donors did not bring about inhibition of tumor growth in the secondary hosts of his experiments; in fact, there was evidence that the test grafts grew more rapidly in those mice than in the control recipients.…”

Section: The Transfer Of the Pre-injection E~ect By Lymph Node Cellsmentioning

confidence: 93%

Studies on the Transfer of Lymph Node Cells

Harris

Farber

1958

A previous communication described the effects of pre-injection of rabbit blood leucocytes in experiments involving the homologous transfer of rabbit lymph node ceils. It was reported there that the usual appearance of antibodies in the sera of the recipient rabbits, after transfer of antigen-incubated lymph node cells, did not occur if leucocytes obtained from the donor animals were injected into the recipients at an appropriate interval prior to cell transfer. Several observations suggested that this effect of the pre-injection of leucocytes was immunologic in nature, involving tissue antigens of rabbit leucocytes: the time interval required between leucocyte pre-injection and lymph node cell transfer, the ineffectiveness of the pre-injection of leucocytes obtained from several other mammalian species, and the effectiveness of leucocytes pooled from other rabbits, and even of some other individual rabbits , but not of leucocytes obtained from the recipient animal itself (1).Accordingly, further studies were undertaken which bear on an immunologic mechanism of the pre-injection effect? First, since in terms of an immunologic mechanism the pre-injection effect would be due to an antigenic stimulus by the pre-injected leucocytes, experiments were done to see whether x-irradiation prior to that injection would inhibit the effect. Second, transfer of the preinjection effect was undertaken by the use of cells from lymph nodes draining sites of injection of rabbit leucocytes. Finally, experiments were carried out on the passive transfer of the pre-injection effect by rabbit-anti-rabbit-leucocyte serum.

“…(Received for publication, March 24, 1955) In preceding papers (1)(2)(3) it has been shown that heightened resistance to certain tumor homografts in mice can be transferred to secondary hosts by lymph node cells, but not by serum. Similar results have been reported by Billingham,Brent,and Medawar (4), with resistance to homografts of skin.…”

mentioning

confidence: 99%

Studies on the Immunological Response to Foreign Tumor Transplants in the Mouse

Mitchison

Dube

1955

Self Cite

108

The relation between serum antibody and resistance to tumor homografts in the mouse has been investigated. Production of serum antibody in response to homografts of a transplantable sarcoma (Sarcoma 1) was demonstrated, by cytotoxic action on the cells of the tumor, and also by a hemagglutinin test. The simpler and more repeatable hemagglutinin test was further investigated. Peak hemagglutinin titres were reached after the immunizing homografts underwent breakdown. Following transfer of lymph node cells from immunized mice into hosts of the same strain, hemagglutinin could be detected in the host serum. The course of its production showed that this secondary antibody was not elicited by transferred antigen, nor could it be due to transfer of preformed antibody. The cells developed the capacity to transfer hemagglutinin production later than the power to transfer heightened graft resistance. Spleen cells also transferred hemagglutinin production, at a later stage after immunization and to a lesser extent than cells from the regional lymph nodes. Implantation of the sarcoma in mice pretreated with certain preparations of lyophilized or frozen tissue stimulated hemagglutinin production, although the tumor grew progressively. The regional lymph nodes participated in the response: they could transfer hemagglutinin production into secondary hosts, but not graft resistance, and indeed appeared to diminish resistance. Lymph node cells from immunized donors conferred protection against the tumor on pretreated mice. Lymph nodes from normal donors also appeared in some experiments to confer protection although the effect was obscured by the rapidity with which the growing tumor became immunologically invulnerable. The fate of lymph node cells stained with acriflavine was followed after transfer. No effect of the staining on the power of the cells to confer immunity could be detected. Cells transferred to the peritoneal cavity passed into various host tissues, but were not found in test homografts. The conclusion is drawn that the hemagglutinating antibody is distinct from the antibody effective in combating homografts. The similarity in this respect between the homograft reaction and sensitization is emphasized in discussion.