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. 1971 Mar 31;133(4):821–833. doi: 10.1084/jem.133.4.821

REJECTION OF TUMOR ALLOGRAFTS BY MOUSE SPLEEN CELLS SENSITIZED IN VITRO

Irun R Cohen 1, Amiela Globerson 1, Michael Feldman 1
PMCID: PMC2138967  PMID: 5547058

Abstract

This paper reports a model system of cellular immunity in which allosensitization of mouse spleen cells is induced in vitro. Allosensitization was achieved by culturing spleen cells upon monolayers of allogeneic fibroblasts. The ability of the spleen cells to inhibit the growth of tumor allografts in vivo served as a functional assay of sensitization. We found that unsensitized spleen cells or spleen cells sensitized against unrelated fibroblast antigens had no inhibitory effect on the growth of allogeneic fibrosarcoma cells when they were injected together into irradiated recipients. In contrast, spleen cells which were specifically allosensitized in vitro were found to be highly effective in inhibiting the growth of an equal number of allogeneic tumor cells. Several times more spleen cells from mice sensitized in vivo were required to produce a similar immune effect. This confirms the findings of previous studies which indicate that sensitization in cell culture can promote the selection of specifically sensitized lymphocytes. Preincubating sensitizing fibroblasts with allo-antisera blocked the allosensitization of spleen cells. This suggests that antibodies binding to fibroblasts may inhibit the induction of sensitization by competing with lymphocytes for antigenic sites. Mouse spleen cells which were able to recognize and reject tumor allografts in vivo were unable to cause lysis of target fibroblasts in vitro. Such fibroblasts, however, were susceptible to lysis by rat lymphoid cells sensitized by a similar in vitro method. These findings indicate that the conditions required for lymphocyte-mediated lysis of target cells may not be directly related to the processes of antigen recognition and allograft rejection in vivo.

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Selected References

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

  1. Berke G., Ax W., Ginsburg H., Feldman M. Graft reaction in tissue culture. II. Quantification of the lytic action on mouse fibroblasts by rat lymphocytes sensitized on mouse embryo monolayers. Immunology. 1969 May;16(5):643–657. [PMC free article] [PubMed] [Google Scholar]
  2. Brent L., Medawar P. B. Cellular immunity and the homograft reaction. Br Med Bull. 1967 Jan;23(1):55–60. doi: 10.1093/oxfordjournals.bmb.a070517. [DOI] [PubMed] [Google Scholar]
  3. Brondz B. D. Complex specificity of immune lymphocytes in allogeneic cell cultures. Folia Biol (Praha) 1968;14(2):115–131. [PubMed] [Google Scholar]
  4. Brunner K. T., Mauel J., Rudolf H., Chapuis B. Studies of allograft immunity in mice. I. Induction, development and in vitro assay of cellular immunity. Immunology. 1970 Apr;18(4):501–515. [PMC free article] [PubMed] [Google Scholar]
  5. Cohen I. R., Stavy L., Feldman M. Glucocorticoids and cellular immunity in vitro. Facilitation of the sensitization phase and inhibition of the effector phase of a lymphocyte anti-fibroblast reaction. J Exp Med. 1970 Dec 1;132(6):1055–1070. doi: 10.1084/jem.132.6.1055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. FELDMAN M., GLOBERSON A., YAFFE D. Immunological properties of chemically induced sarcomas. Acta Unio Int Contra Cancrum. 1963;19:65–72. [PubMed] [Google Scholar]
  7. GLOBERSON A., FELDMAN M. ROLE OF THE THYMUS IN RESTORATION OF IMMUNE REACTIVITY AND LYMPHOID REGENERATION IN IRRADIATED MICE. Transplantation. 1964 Mar;2:212–227. doi: 10.1097/00007890-196403000-00006. [DOI] [PubMed] [Google Scholar]
  8. Ginsburg H. Graft versus host reaction in tissue culture. I. Lysis of monolayers of embryo mouse cells from strains differing in the H-2 histocompatibility locus by rat lymphocytes sensitized in vitro. Immunology. 1968 May;14(5):621–635. [PMC free article] [PubMed] [Google Scholar]
  9. Hellström K. E., Hellström I. Cellular immunity against tumor antigens. Adv Cancer Res. 1969;12:167–223. doi: 10.1016/s0065-230x(08)60331-0. [DOI] [PubMed] [Google Scholar]
  10. Holm G., Perlmann P. Cytotoxic potential of stimulated human lymphocytes. J Exp Med. 1967 Apr 1;125(4):721–736. doi: 10.1084/jem.125.4.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lonai P., Feldman M. Cooperation of lymphoid cells in an in vitro graft reaction system. The role of the thymus cell. Transplantation. 1970 Nov;10(5):372–381. doi: 10.1097/00007890-197011000-00003. [DOI] [PubMed] [Google Scholar]
  12. Mauel J., Rudolf H., Chapuis B., Brunner K. T. Studies of allograft immunity in mice. II. Mechanism of target cell inactivation in vitro by sensitized lymphocytes. Immunology. 1970 Apr;18(4):517–535. [PMC free article] [PubMed] [Google Scholar]
  13. Perlmann P., Holm G. Cytotoxic effects of lymphoid cells in vitro. Adv Immunol. 1969;11:117–193. doi: 10.1016/s0065-2776(08)60479-4. [DOI] [PubMed] [Google Scholar]
  14. Wilson D. B. Lymphocytes as mediators of cellular immunity: destruction of homologous target cells in culture. Transplantation. 1967 Jul;5(4 Suppl):986–988. [PubMed] [Google Scholar]

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