Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1980 Oct 1;152(4):823–841. doi: 10.1084/jem.152.4.823

Elimination of syngeneic sarcomas in rats by a subset of T lymphocytes

PMCID: PMC2185982  PMID: 6968337

Abstract

Established subcutaneous Moloney sarcomas (MST-1) of large size and long duration were eliminated from syngeneic rats by intravenous infusion of varying numbers of specific syngeneic effector T lymphocytes. Spleen cells from BN rats in which tumor had regressed were cultured in an in vitro mixed lymphocyte tumor cell culture (MLTC) to augment cytotoxicity of effector cells. In the MLTC a T cell subset was expanded in response to MST-1 antigens and transformed into blast elements. With these changes, there was an increase in the W3/25 antigen on the T cell surface, a decrease of W3/13 antigen, and an increase in the number of T cells with Ia antigens. The subset associated with elimination of established tumors was a blast T cell W3/25+, W3/13+, as detected by monoclonal antibodies to rat T antigens. The W3/25+ subset was poorly cytotoxic in vitro for MST-1 and apparently functioned in vivo as an amplifier or helper cell in the tumor-bearing host. The W3/25- population was a melange of cells that included (W3/13+, W3/25-) T cells, null cells, Ig+ cells, and macrophages, and was associated with enhancement of tumor in vivo, suggesting the presence of suppressor cells.

Full Text

The Full Text of this article is available as a PDF (2.0 MB).

Selected References

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

  1. Alexander P., Connell D. I., Mikulska Z. B. Treatment of a murine leukemia with spleen cells or sera from allogeneic mice immunized against the tumor. Cancer Res. 1966 Jul;26(7):1508–1515. [PubMed] [Google Scholar]
  2. Alexander P. Immunotherapy of leukemia: the use of different classes of immune lymphocytes. Cancer Res. 1967 Dec;27(12):2521–2526. [PubMed] [Google Scholar]
  3. Balch C. M., Feldman J. D. Thymus-dependent (T) lymphocytes in the rat. J Immunol. 1974 Jan;112(1):79–86. [PubMed] [Google Scholar]
  4. Berendt M. J., North R. J., Kirstein D. P. The immunological basis of endotoxin-induced tumor regression. Requirement for T-cell-mediated immunity. J Exp Med. 1978 Dec 1;148(6):1550–1559. doi: 10.1084/jem.148.6.1550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berendt M. J., North R. J. T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor. J Exp Med. 1980 Jan 1;151(1):69–80. doi: 10.1084/jem.151.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bernstein I. D. Passive transfer of systemic tumor immunity with cells generated in vitro by a secondary immune response to a syngeneic rat gross virus-induced lymphoma. J Immunol. 1977 Jan;118(1):122–128. [PubMed] [Google Scholar]
  7. Bernstein I. D., Wright P. W., Cohen E. Generation of cytotoxic lymphocytes in vitro: response of immune rat spleen cells to a syngeneic gross virus-induced lymphoma in mixed lymphocyte-tumor culture. J Immunol. 1976 May;116(5):1367–1372. [PubMed] [Google Scholar]
  8. Blasecki J. W., Tevethia S. S. Restoration of specific immunity against SV40 tumor-specific transplantation antigen to lymphoid cells from tumor-bearing mice. Int J Cancer. 1975 Aug 15;16(2):275–283. doi: 10.1002/ijc.2910160210. [DOI] [PubMed] [Google Scholar]
  9. Borberg H., Oettgen H. F., Choudry K., Beattie E. J., Jr Inhibition of established transplants of chemically induced sarcomas in syngeneic mice by lymphocytes from immunized donors. Int J Cancer. 1972 Nov;10(3):539–547. doi: 10.1002/ijc.2910100312. [DOI] [PubMed] [Google Scholar]
  10. Bortin M. M., Rose W. C., Truitt R. L., Rimm A. A., Saltzstein E. C., Rodey G. E. Graft versus leukemia. VI. Adoptive immunotherapy in combination with chemoradiotherapy for spontaneous leukemia-lymphoma in AKR mice. J Natl Cancer Inst. 1975 Nov;55(5):1227–1229. doi: 10.1093/jnci/55.5.1227. [DOI] [PubMed] [Google Scholar]
  11. Bruce J., Mitchison N. A., Shellam G. R. Studies on a gross-virus-induced lymphoma in the rat. III. Optimisation, specificity and applications of the in vitro immune response. Int J Cancer. 1976 Mar 15;17(3):342–350. doi: 10.1002/ijc.2910170310. [DOI] [PubMed] [Google Scholar]
  12. Cheever M. A., Greenberg P. D., Fefer A. Tumor neutralization, immunotherapy, and chemoimmunotherapy of a Friend leukemia with cells secondarily sensitized in vitro: II. Comparison of cells cultured with and without tumor to noncultured immune cells. J Immunol. 1978 Dec;121(6):2220–2227. [PubMed] [Google Scholar]
  13. Dullens H. F., Den Otter W. Therapy with allogeneic immune peritoneal cells. Cancer Res. 1974 Jul;34(7):1726–1730. [PubMed] [Google Scholar]
  14. Evans R. L., Faldetta T. J., Humphreys R. E., Pratt D. M., Yunis E. J., Schlossman S. F. Peripheral human T cells sensitized in mixed leukocyte culture synthesize and express Ia-like antigens. J Exp Med. 1978 Nov 1;148(5):1440–1445. doi: 10.1084/jem.148.5.1440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fass L., Fefer A. Studies of adoptive chemoimmunotherapy of a Friend virus-induced lymphoma. Cancer Res. 1972 May;32(5):997–1001. [PubMed] [Google Scholar]
  16. Fefer A. Adoptive chemoimmunotherapy of a Moloney lymphoma. Int J Cancer. 1971 Nov 15;8(3):364–373. doi: 10.1002/ijc.2910080303. [DOI] [PubMed] [Google Scholar]
  17. Fefer A., Einstein A. B., Cheever M. A. Adoptive chemoimmunotherapy of cancer in animals: a review of results, principles, and problems. Ann N Y Acad Sci. 1976;277(00):492–504. doi: 10.1111/j.1749-6632.1976.tb41723.x. [DOI] [PubMed] [Google Scholar]
  18. Fefer A. Immunotherapy and chemotherapy of Moloney sarcoma virus-induced tumors in mice. Cancer Res. 1969 Dec;29(12):2177–2183. [PubMed] [Google Scholar]
  19. Fefer A., McCoy J. L., Glynn J. P. Studies on the growth and regression of a transplantable Moloney sarcoma. Cancer Res. 1967 Nov;27(11):2207–2211. [PubMed] [Google Scholar]
  20. Fefer A. Treatment of a Moloney lymphoma with cyclophosphamide and H-2-incompatible spleen cells. Cancer Res. 1973 Apr;33(4):641–644. [PubMed] [Google Scholar]
  21. Fernandez-Cruz E., Halliburton B., Feldman J. D. In vivo elimination by specific effector cells of an established syngeneic rat moloney virus-induced sarcoma. J Immunol. 1979 Oct;123(4):1772–1777. [PubMed] [Google Scholar]
  22. Fisher J. C., Hammond W. G. Inhibition of tumor growth by syngeneic spleen cell transfer. Surg Forum. 1966;17:102–104. [PubMed] [Google Scholar]
  23. Freedman L. R., Cerottini J. C., Brunner K. T. In vivo studies of the role of cytotoxic T cells in tumor allograft immunity. J Immunol. 1972 Dec;109(6):1371–1378. [PubMed] [Google Scholar]
  24. Fu S. M., Chiorazzi N., Wang C. Y., Montrazeri G., Kunkel H. G., Ko H. S., Gottlieb A. B. Ia-bearing T lymphocytes in man. Their identification and role in the generation of allogeneic helper activity. J Exp Med. 1978 Nov 1;148(5):1423–1428. doi: 10.1084/jem.148.5.1423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Gillis S., Baker P. E., Ruscetti F. W., Smith K. A. Long-term culture of human antigen-specific cytotoxic T-cell lines. J Exp Med. 1978 Oct 1;148(4):1093–1098. doi: 10.1084/jem.148.4.1093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Gillis S., Smith K. A. In vitro generation of tumor-specific cytotoxic lymphocytes. Secondary allogeneic mixed tumor lymphocyte culture of normal murine spleen cells. J Exp Med. 1977 Aug 1;146(2):468–482. doi: 10.1084/jem.146.2.468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Glaser M., Lavrin D. H., Herberman R. B. In vivo protection against syngeneic Gross virus-induced lymphoma in rats: comparison with in vitro studies of cell-mediated immunity. J Immunol. 1976 Jun;116(6):1507–1511. [PubMed] [Google Scholar]
  28. Glynn J. P., Halpern B. L., Fefer A. An immunochemotherapeutic system for the treatment of a transplanted Moloney virus-induced lymphoma in mice. Cancer Res. 1969 Mar;29(3):515–520. [PubMed] [Google Scholar]
  29. Gorczynski R. M. Evidence for in vivo protection against murine-sarcoma virus-induced tumors by T lymphocytes from immune animals. J Immunol. 1974 Feb;112(2):533–539. [PubMed] [Google Scholar]
  30. Gorczynski R. M., Norbury C. Immunity to murine sarcoma virus induced tumours. 3. Analysis of the cell populations involved in protection from lethal tumour progression of sublethally irradiated, MSV inoculated, mice. Br J Cancer. 1974 Aug;30(2):118–128. doi: 10.1038/bjc.1974.122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Howell S. B., Dean J. H., Esber E. C., Llaw L. W. Cell interactions in adoptive immune rejection of a syngeneic tumor. Int J Cancer. 1974 Nov 15;14(5):662–674. doi: 10.1002/ijc.2910140514. [DOI] [PubMed] [Google Scholar]
  32. Jones J. M., Jensen F., Veit B., Feldman J. D. In vivo growth and antigenic properties of a rat sarcoma induced by Moloney sarcoma virus. J Natl Cancer Inst. 1974 Jun;52(6):1771–1777. doi: 10.1093/jnci/52.6.1771. [DOI] [PubMed] [Google Scholar]
  33. Kasakura S. Lymphocyte soluble factor-activated cell-mediated cytotoxicity: the role of Ia-like antigens in activation and cytolysis, and their relationship to Fc receptor. J Immunol. 1979 Mar;122(3):1166–1171. [PubMed] [Google Scholar]
  34. Kedar E., Schwartzbach M., Raanan Z., Hefetz S. In vitro induction of cell-mediated immunity to murine leukemia cells. II. cytotoxic activity in vitro and tumor-neutralizing capacity in vivo of anti-leukemia cytotoxic lymphocytes generated in macrocultures. J Immunol Methods. 1977;16(1):39–58. doi: 10.1016/0022-1759(77)90038-2. [DOI] [PubMed] [Google Scholar]
  35. Ko H. S., Fu S. M., Winchester R. J., Yu D. T., Kunkel H. G. Ia determinants on stimulated human T lymphocytes. Occurrence on mitogen- and antigen-activated T cells. J Exp Med. 1979 Aug 1;150(2):246–255. doi: 10.1084/jem.150.2.246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Leclerc J. C., Cantor H. T cell-mediated immunity to oncornavirus-induced tumors. I. Ly phenotype of precursor and effector cytolytic T lymphocytes. J Immunol. 1980 Feb;124(2):846–850. [PubMed] [Google Scholar]
  37. Lukasewycz O. A., Duffey P. S., Murphy W. H. Immune mechanisms in leukemia: protective capacity of the major lymphoid cell compartments. J Immunol. 1976 Apr;116(4):976–981. [PubMed] [Google Scholar]
  38. Lukasewycz O. A., Martinez D., Murphy W. H. Immune mechanisms in leukemia: evaluation of immunocompetent cell populations. J Immunol. 1975 May;114(5):1491–1496. [PubMed] [Google Scholar]
  39. Mage M. G., McHugh L. L., Rothstein T. L. Mouse lymphocytes with and without surface immunoglobulin: preparative scale separation in polystyrene tissue culture dishes coated with specifically purified anti-immunoglobulin. J Immunol Methods. 1977;15(1):47–56. doi: 10.1016/0022-1759(77)90016-3. [DOI] [PubMed] [Google Scholar]
  40. Matter A., Askonas B. A. Protection against murine ascites tumours by lymphoid cell populations with T memory or cytotoxicity. Transplantation. 1976 Aug;22(2):184–189. doi: 10.1097/00007890-197608000-00014. [DOI] [PubMed] [Google Scholar]
  41. Mihich E. Combined effects of chemotherapy and immunity against leukemia L1210 in DBA-2 mice. Cancer Res. 1969 Apr;29(4):848–854. [PubMed] [Google Scholar]
  42. Perry L. L., Dorf M. E., Benacerraf B., Greene M. I. Regulation of immune response to tumor antigen: interference with syngeneic tumor immunity by anti-IA alloantisera. Proc Natl Acad Sci U S A. 1979 Feb;76(2):920–924. doi: 10.1073/pnas.76.2.920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Putman D. L., Kind P. D., Goldin A., Kende M. Adoptive immunochemotherapy of a transplantable AKR leukemia (K36). Int J Cancer. 1978 Feb 15;21(2):230–233. doi: 10.1002/ijc.2910210215. [DOI] [PubMed] [Google Scholar]
  44. Reinherz E. L., Kung P. C., Pesando J. M., Ritz J., Goldstein G., Schlossman S. F. Ia determinants on human T-cell subsets defined by monoclonal antibody. Activation stimuli required for expression. J Exp Med. 1979 Dec 1;150(6):1472–1482. doi: 10.1084/jem.150.6.1472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Rosenberg S. A., Terry W. D. Passive immunotherapy of cancer in animals and man. Adv Cancer Res. 1977;25:323–388. doi: 10.1016/s0065-230x(08)60637-5. [DOI] [PubMed] [Google Scholar]
  46. Rouse B. T., Röllinghoff M., Warner N. L. Tumor immunity to murine plasma cell tumors. II. Essential role of T lymphocytes in immune response. Eur J Immunol. 1973 Apr;3(4):218–224. doi: 10.1002/eji.1830030408. [DOI] [PubMed] [Google Scholar]
  47. Rouse B. T., Wagner H., Harris A. W. In vivo activity of in vitro immunized lymphocytes. I. Tumor allograft rejection mediated by in vitro activated mouse thymocytes. J Immunol. 1972 May;108(5):1353–1361. [PubMed] [Google Scholar]
  48. Röllinghoff M., Wagner H. Brief communication: In vivo protection against murine plasma cell tumor growth by in vitro activated syngeneic lymphocytes. J Natl Cancer Inst. 1973 Oct;51(4):1317–1318. doi: 10.1093/jnci/51.4.1317. [DOI] [PubMed] [Google Scholar]
  49. Röllinghoff M., Wagner H. In vitro induction of tumor specific immunity: requirements for T lymphocytes and tumor growth inhibition in vivo. Eur J Immunol. 1973 Aug;3(8):471–476. doi: 10.1002/eji.1830030804. [DOI] [PubMed] [Google Scholar]
  50. Sachs D. H., Humphrey G. W., Lunney J. K. Sharing of Ia antigens between species. I. Detection of Ia specificities shared by rats and mice. J Exp Med. 1977 Aug 1;146(2):381–393. doi: 10.1084/jem.146.2.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Schirrmacher V. Tumor metastases and cell-mediated immunity in a model system in DBA/2 mice. V. Transfer of protective immunity with H-2 identical immune T cells from B10.D2 mice. Int J Cancer. 1979 Jul 15;24(1):80–86. doi: 10.1002/ijc.2910240114. [DOI] [PubMed] [Google Scholar]
  52. Small M., Trainin N. Inhibition of syngeneic fibrosarcoma growth by lymphocytes sensitized on tumor-cell monolayers in the presence of the thymic humoral factor. Int J Cancer. 1975 Jun 15;15(6):962–972. doi: 10.1002/ijc.2910150612. [DOI] [PubMed] [Google Scholar]
  53. Smith H. G., Harmel R. P., Hanna M. G., Jr, Zwilling B. S., Zbar B., Rapp H. J. Regression of established intradermal tumors and lymph node metastases in guinea pigs after systemic transfer of immune lymphoid cells. J Natl Cancer Inst. 1977 May;58(5):1315–1322. doi: 10.1093/jnci/58.5.1315. [DOI] [PubMed] [Google Scholar]
  54. Swierkosz J. E., Marrack P., Kappler J. W. Functional analysis of T cells expressing Ia antigens. I. Demonstration of helper T-cell heterogeneity. J Exp Med. 1979 Dec 1;150(6):1293–1309. doi: 10.1084/jem.150.6.1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Takeichi N., Kuzumaki N., Kodama T., Kobayashi H., Boone C. W. Adoptive immunotherapy of a Gross virus producing lymphoma and a methylcholanthrene-induced fibrosarcoma in tolerant rats. Cancer Res. 1976 Nov;36(11 Pt 1):4039–4043. [PubMed] [Google Scholar]
  56. Tevethia S. S., Blasecki J. W., Waneck G., Goldstein A. L. Requirement of thymus-derived theta-positive lymphocytes for rejection of DNA virus (SV 40) tumors in mice. J Immunol. 1974 Nov;113(5):1417–1423. [PubMed] [Google Scholar]
  57. Ting C. C., Rodrigues D., Igarashi T. Studies of the mechanisms for the induction of in vivo tumor immunity. III. Recruitment of host helper cells by donor T cells in adoptive transfer of cell-mediated immunity. J Immunol. 1979 Apr;122(4):1510–1518. [PubMed] [Google Scholar]
  58. Treves A. J., Cohen I. R., Feldman M. Immunotherapy of lethal metastases by lymphocytes sensitized against tumor cells in vitro. J Natl Cancer Inst. 1975 Mar;54(3):777–780. [PubMed] [Google Scholar]
  59. Treves A. J., Cohen I. R., Schechter B., Feldman M. In vivo effects of lymphocytes sensitized in vitro against tumor cells. Ann N Y Acad Sci. 1976;276:165–175. doi: 10.1111/j.1749-6632.1976.tb41644.x. [DOI] [PubMed] [Google Scholar]
  60. Tucker D. F., Dennert G., Lennox E. S. Thymus-derived lymphocytes as effectors of cell-mediated immunity to syngeneic and allogeneic transplants in the rat. J Immunol. 1974 Oct;113(4):1302–1312. [PubMed] [Google Scholar]
  61. Vadlamudi S., Padarathsingh M., Bonmassar E., Goldin A. Effect of combination treatment with cyclophosphamide and isogeneic or allogeneic spleen and bone marrow cells in leukemic (L1210) mice. Int J Cancer. 1971 Jan 15;7(1):160–166. doi: 10.1002/ijc.2910070118. [DOI] [PubMed] [Google Scholar]
  62. WOODRUFF M. F., BOAK J. L. INHIBITORY EFFECT OF PRE-IMMUNIZED CBA SPLEEN CELLS ON TRANSPLANTS OF A-STRAIN MOUSE MAMMARY CARCINOMA IN (CBA X A) F1 HYBRID RECIPIENTS. Br J Cancer. 1965 Jun;19:411–417. doi: 10.1038/bjc.1965.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Wepsic H. T., Kronman B. S., Zbar B., Borsos T., Rapp H. J. Immunotherapy of an intramuscular tumor in strain-2 guinea pigs: prevention of tumor growth by intradermal immunization and by systemic transfer of tumor immunity. J Natl Cancer Inst. 1970 Aug;45(2):377–386. [PubMed] [Google Scholar]
  64. Wepsic H. T., Zbar B., Rapp H. J., Borsos T. Systemic transfer of tumor immunity: delayed hypersensitivity and suppression of tumor growth. J Natl Cancer Inst. 1970 Apr;44(4):955–963. [PubMed] [Google Scholar]
  65. White R. A., Mason D. W., Williams A. F., Galfre G., Milstein C. T-lymphocyte heterogeneity in the rat: separation of functional subpopulations using a monoclonal antibody. J Exp Med. 1978 Sep 1;148(3):664–673. doi: 10.1084/jem.148.3.664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Williams A. F., Galfrè G., Milstein C. Analysis of cell surfaces by xenogeneic myeloma-hybrid antibodies: differentiation antigens of rat lymphocytes. Cell. 1977 Nov;12(3):663–673. doi: 10.1016/0092-8674(77)90266-5. [DOI] [PubMed] [Google Scholar]
  67. Woda B. A., Feldman J. D. Density of surface immunoglobulin and capping on rat B lymphocytes. I. Changes with aging. J Exp Med. 1979 Feb 1;149(2):416–423. doi: 10.1084/jem.149.2.416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Woda B. A., Yguerabide J., Feldman J. D. Mobility and density of AgB, "Ia", and Fc receptors on the surface of lymphocytes from young and old rats. J Immunol. 1979 Nov;123(5):2161–2167. [PubMed] [Google Scholar]
  69. Zarling J. M., Bach F. H. Continuous culture of T cells cytotoxic for autologous human leukaemia cells. Nature. 1979 Aug 23;280(5724):685–688. doi: 10.1038/280685a0. [DOI] [PubMed] [Google Scholar]
  70. Zarling J. M., Tevethia S. S. Transplantation immunity to simian virus 40-transformed cells in tumor-bearing mice. I. Development of cellular immunity to simian virus 40 tumor-specific transplantation antigens during tumorigenesis by transplanted cells. J Natl Cancer Inst. 1973 Jan;50(1):137–147. doi: 10.1093/jnci/50.1.137. [DOI] [PubMed] [Google Scholar]
  71. van Loveren H., den Otter W. In vitro activation of armed macrophages and the therapeutic application in mice. J Natl Cancer Inst. 1974 Jun;52(6):1917–1918. doi: 10.1093/jnci/52.6.1917. [DOI] [PubMed] [Google Scholar]

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

RESOURCES