Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1960 Aug 1;112(2):293–314. doi: 10.1084/jem.112.2.293

DEPRESSION BY ANTIBODY OF THE IMMUNE RESPONSE TO HOMOGRAFTS AND ITS ROLE IN IMMUNOLOGICAL ENHANCEMENT

George D Snell 1, Henry J Winn 1, Jack H Stimpfling 1, Stephen J Parker 1
PMCID: PMC2137227  PMID: 19867173

Abstract

This paper reports tests of two hypotheses that have been proposed to account for the enhanced growth of tumor homografts in the presence of antiserum reactive with the graft (immunological enhancement). According to the first hypothesis, enhancement is due to some "physiological" alteration in the tumor, induced by its contact with antiserum, which insures its survival despite the hostile response of the host. According to the second hypothesis, antiserum alters the response of the host. By blocking the development of the cellular type of immunity, which is the main agent in graft destruction, it permits the graft to survive. To test hypothesis 1, strain A tumor SaI was passed from A's, and from enhanced B10.D2's, into untreated B10.D2's. The per cent of deaths was essentially the same in both groups (48 and 44 per cent, respectively); there was no evidence that passage through enhanced B10.D2's altered the capacity of the tumor to grow in the foreign strain. Several other groups of mice included in the experiment all confirmed this conclusion. The experiment failed to confirm hypothesis 1. In the tests of hypothesis 2, the effect of isoantiserum on immune responses of both the humoral and cellular type was measured. When antiserum was given together with foreign strain lymphoid cells (antigen), almost no additional antibody was manufactured; in contrast with this, controls receiving foreign cells only produced red cell agglutinating antibody in high titer. The effect of antiserum on the development of immunity of the cellular type was tested by the method of Winn. In this assay, presumptively immune node cells, in various dilutions, are mixed with tumor cells and injected into appropriate mice. Immunity is indicated by inhibited tumor growth. Antiserum given at the same time as a tumor homograft greatly depressed the immunity of the cells expressed from the draining nodes. At 6 days after the graft, the level of immunity of cells from treated mice was 1/24th to 1/32nd that of cells from controls receiving tumor alone. The same sort of depressing effect was noted when the immunizing tissue was foreign thymus or embryo. Antiserum given 1 or more days after the immunizing tissue also resulted in a lower level of cellular immunity (but the assay used in this case was a less critical one). These results provide an adequate explanation of the phenomenon of immunological enhancement, at least as it occurs in the particular test system used in these experiments. Since it is cellular immunity rather than humoral antibody that inhibits the growth of most grafts (transplantable leukemias are an exception), the depression of this immunity by antibody is favorable to the growth of a homograft.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BARRETT M. K., HANSEN W. H. Undulations in the time-response curve for tumor immunity after primary immunization with washed erythrocytes. J Natl Cancer Inst. 1957 Jan;18(1):57–63. [PubMed] [Google Scholar]
  2. GORER P. A., MIKULSKA Z. B. The antibody response to tumor inoculation; improved methods of antibody detection. Cancer Res. 1954 Oct;14(9):651–655. [PubMed] [Google Scholar]
  3. GORER P. A. Some reactions of H-2 antibodies in vitro and in vivo. Ann N Y Acad Sci. 1958 Oct 7;73(3):707–721. doi: 10.1111/j.1749-6632.1959.tb40848.x. [DOI] [PubMed] [Google Scholar]
  4. GREEN H. N. The absence of immunological identity in neoplastic cells. Ann N Y Acad Sci. 1957 Oct 21;68(2):268–301. doi: 10.1111/j.1749-6632.1957.tb56086.x. [DOI] [PubMed] [Google Scholar]
  5. GREEN H. N., WILSON R. Further observations on tumour-enhancing factors: their bearing on the immunological theory of cancer. Nature. 1958 Oct 18;182(4642):1054–1058. doi: 10.1038/1821054a0. [DOI] [PubMed] [Google Scholar]
  6. HOLLAND J. J., PICKETT M. J. A cellular basis of immunity in experimental Brucella infection. J Exp Med. 1958 Sep 1;108(3):343–360. doi: 10.1084/jem.108.3.343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. KALISS N. Acceptance of tumor homografts by mice injected with antiserum. II. Effect of time of injection. Proc Soc Exp Biol Med. 1956 Mar;91(3):432–437. doi: 10.3181/00379727-91-22285. [DOI] [PubMed] [Google Scholar]
  8. KALISS N. Immunological enhancement of tumor homografts in mice: a review. Cancer Res. 1958 Oct;18(9):992–1003. [PubMed] [Google Scholar]
  9. KALISS N., KANDUTSCH A. A. Acceptance of tumor homografts by mice injected with antiserum. I. Activity of serum fractions. Proc Soc Exp Biol Med. 1956 Jan;91(1):118–121. doi: 10.3181/00379727-91-22185. [DOI] [PubMed] [Google Scholar]
  10. Kaliss N. COURSE OF PRODUCTION OF AN ISOANTISERUM EFFECTING TUMOR HOMOGRAFT SURVIVAL IN MICE. Proc Natl Acad Sci U S A. 1956 May;42(5):269–273. doi: 10.1073/pnas.42.5.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. METCALF D. The thymic origin of the plasma lymphocytosis stimulating factor. Br J Cancer. 1956 Sep;10(3):442–457. doi: 10.1038/bjc.1956.51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. MITCHISON N. A. Studies on the immunological response to foreign tumor transplants in the mouse. I. The role of lymph node cells in conferring immunity by adoptive transfer. J Exp Med. 1955 Aug 1;102(2):157–177. doi: 10.1084/jem.102.2.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. SNELL G. D. A cytosieve permitting sterile preparation of suspensions of tumor cells for transplantation. J Natl Cancer Inst. 1953 Jun;13(6):1511–1515. [PubMed] [Google Scholar]
  14. SNELL G. D. Histocompatibility genes of the mouse. I. Demonstration of weak histocompatibility differences by immunization and controlled tumor dosage. J Natl Cancer Inst. 1958 Apr;20(4):787–824. [PubMed] [Google Scholar]
  15. SNELL G. D., JACKSON R. B. Histocompatibility genes of the mouse. II. Production and analysis of isogenic resistant lines. J Natl Cancer Inst. 1958 Nov;21(5):843–877. [PubMed] [Google Scholar]
  16. SNELL G. D. The homograft reaction. Annu Rev Microbiol. 1957;11:439–458. doi: 10.1146/annurev.mi.11.100157.002255. [DOI] [PubMed] [Google Scholar]
  17. WINN H. J. The immune response and the homograft reaction. Natl Cancer Inst Monogr. 1960 Mar;2:113–138. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES