Skip to main content
NCBI home page
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1988 Jan;79(1):91–98. doi: 10.1111/j.1349-7006.1988.tb00015.x

Mediation of in vivo Tumor‐neutralizing Activity by Lyt‐2+ as Well as L3T4+ T Cell Subsets*1

Takayuki Yoshioka 1, Soichiro Sato 1, Masato Ogata 1, Kohichi Sakamoto 1, Haruo Sano 1, Junko Shima 1, Hiroshi Yamamoto 2, Hiromi Fujiwara ✉, Toshiyuki Hamaoka 1
PMCID: PMC5907754  PMID: 2965692

Abstract

The present study reexamines the cell surface nature of T cells mediating in vivo protective tumor immunity with the use of anti‐L3T4 and ‐Lyt‐2 antibodies. C3H/HeN mice hyperimmune against syngeneic MH134 hepatoma or MCH‐1‐A1 fibrosarcoma were prepared by intradermal (id) inoculation of viable tumor cells followed by surgical resection of the tumor and by repeated challenges with viable tumor cells. Spleen cells from these mice were fractionated into L3T4+ or Lyt‐2+ T cell subset by treatment with anti‐Lyt‐2 or ‐L3T4 antibody plus complement (C). Winn assays performed by utilizing such fractionated T cells have revealed that both L3T4+ and Lyt‐2+ T cell subsets from hyperimmune mice produced complete tumor protection. Flow microfluorometry study illustrated that the treatment with anti‐L3T4 or ‐Lyt‐2 antibody plus C resulted in the complete isolation of L3T4− Lyt‐2+ (Lyt‐2+) or L3T4+ Lyt‐2− (L3T4+) T cell subset, respectively. This contrasted with the failure of treatment with anti‐Lyt‐1 antibody plus C to isolate all T cells expressing Lyt‐2 marker. It was further demonstrated that each subset of T cells exerted its anti‐tumor effect in a tumor‐specific way and without a requirement for the other alternative subpopulation of unprimed T cells. These results indicate that Lyt‐2+ T cell subset can be successfully isolated by treatment with anti‐L3T4 but not with anti‐Lyt‐I antibody plus C, and that each single subset of Lyt‐2+ and L3T4+ T cells can function as in vivo effector T cells.

Keywords: L3T4+ T cell, Lyt‐2+ T cell, Anti‐tumor effect

Full Text

The Full Text of this article is available as a PDF (421.1 KB).

†

This constitutes Part I of a series entitled “Role of tumor‐specific Lyt‐2+ T cells in tumor growth inhibition in vivo.”

REFERENCES

  • 1).Mills , C. D. and North , R. J.Expression of passively transferred immunity against an established tumor depends on generation of cytolytic T cells in recipients. Inhibition by suppressor T cells . J. Exp. Med. , 157 , 1448 – 1460 ( 1983. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2).Rosenstein , M. , Eberlein , T. J. and Rosenberg , S. A.Adoptive immunotherapy of established syngeneic solid tumors: role of T lymphoid subpopulations . J. Immunol. , 132 , 2117 – 2122 ( 1984. ). [PubMed] [Google Scholar]
  • 3).Evans , R.Phenotypes associated with tumor rejection mediated by cyclophosphamide and syngeneic tumor‐sensitized T lymphocytes: potential mechanisms of action . Int. J. Cancer , 33 , 381 – 388 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 4).Dailey , M. O. , Pillemer , E. and Weissman , I. L.Protection against syngeneic lymphoma by a long‐lived cytotoxic T‐cell clone . Proc. Natl. Acad, Sci. USA , 79 , 5384 – 5387 ( 1984. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5).Rosenstein , M. and Rosenberg , S. A.Generation of lytic and proliferative lymphoid clones to syngeneic tumor: in vitro and in vivo studies . J. Natl. Cancer Inst. , 72 , 1161 – 1165 ( 1984. ). [PubMed] [Google Scholar]
  • 6).Yamasaki , T. , Handa , H. , Yamashita , J. , Watanabe , Y. , Namba , Y. and Hanaoka , M.Specific adoptive immunotherapy with tumor‐specific cytotoxic T‐lymphocyte clone for murine malignant gliomas . Cancer Res. , 44 , 1776 – 1783 ( 1984. ). [PubMed] [Google Scholar]
  • 7).Fernandes‐Cruz , E. , Woda , B. A. and Feldman , J. D.Elimination of syngeneic sarcomas in rats by a subset of T lymphocytes . J. Exp. Med. , 152 , 823 – 841 ( 1980. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8).Fujiwara , H. , Fukuzawa , M. , Yoshioka , T. , Nakajima , H. and Hamaoka , T.The role of tumor‐specific Lyt‐l+2− T cells in eradicating tumor cells in vivo. I. Lyt‐l+2− T cells do not necessarily require recruitment of host's cytotoxic T cell precursors for implementation of in vivo immunity . J. Immunol. , 133 , 1671 – 1676 ( 1984. ). [PubMed] [Google Scholar]
  • 9).Fukuzawa , M. , Fujiwara , H. , Yoshioka , T. , Itoh , K. and Hamaoka , T.Tumor‐specific Lyt‐l+2− T cells can reject tumor cells in vivo without inducing cytotoxic T lymphocyte responses . Transplant. Proc. , 17 , 599 – 605 ( 1985. ). [Google Scholar]
  • 10).Greenberg , P. D. , Cheever , M. A. and Fefer , A.Eradication of disseminated murine leukemia by chemoimmunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt‐l+2− lymphocytes . J. Exp. Med. , 154 , 952 – 963 ( 1982. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11).Greenberg , P. H. , Kern , D. E. and Cheever , M. A.Therapy of disseminated murine leukemia with cyclophosphamide and immune Lyt‐l+2+T cells. Tumor eradication does not require participation of cytotoxic T cells . J. Exp. Med. , 161 , 1122 – 1134 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12).Dialynas , D. P. , Quan , Z. S. , Wall , K. A. , Pierres , A. , Quintans , J. , Loken , M. R. , Pierres , M. and Fitch , F. W.Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK‐1.5: similarity of L3T4 to the human Leu‐3/T4 molecule . J. Immunol. , 131 , 2445 – 2451 ( 1983. ). [PubMed] [Google Scholar]
  • 13).Dialynas , D. P. , Wilde , D. B. , Marrack , P. , Pierres , A. , Wall , K. A. , Havran , W. , Otten , G. , Loken , M. R. , Pierres , M. , Kapler , J. and Fitch , F. W.Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen‐reactivity . Immunol. Rev. , 74 , 29 – 56 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 14).Ogata , M. , Shimizu , J. , Tsuchida , T. , Takai , Y. , Fujiwara , H. and Hamaoka , T.Non‐Hlinked genetic regulation of cytotoxic responses to hapten‐modified syngeneic cells. I. Non‐H‐2‐Hnked Ir gene defect expressed on T cells is not predetermined at the stage of bone marrow cells . J. Immunol. , 136 , 1178 – 1185 ( 1986. ). [PubMed] [Google Scholar]
  • 15).Cerottini , J. C. and Brunner , K. T.Cellmediated cytotoxicity, allograft rejection and tumor immunity . Adv. Immunol. , 18 , 67 – 132 ( 1974. ). [DOI] [PubMed] [Google Scholar]
  • 16).Herberman , R. B. , Holden , H. T. , Varesio , L. , Taniyama , T. , Pucetti , P. , Kirchner , H. , Gerson , J. , White , S. , Keisari , Y. and Haskill , J. L.Immunologic reactivity of lymphoid cells in tumors . Contemp. Top. Immunobiol. , 10 , 61 – 78 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 17).Wagner , H. , Hardt , C. , Heeg , K. , Pfissenmaier , K. , Solback , W. , Barlett , R. , Stoskinger , H. and Rollinghoff , M.T‐T cell interactions during cytotoxic T lymphocyte (CTL) responses: T cell derived helper factor (interleukin 2) as a probe to analyze CTL responsiveness and thymic maturation of CTL progenitors . Immunol. Rev. , 51 , 215 – 225 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 18).Leveland , B. E. , Hogarth , P. M. , Geredig , R. H. and Mckenzie , I. F. C.Cells mediating graft rejection in the mouse. I. Lyt‐1 cells mediate skin graft rejection . J. Exp. Med. , 153 , 1044 – 1057 ( 1981. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19).Dallman , M. J. and Mason , D. W.Cellular mechanisms of skin allograft rejection in the rat . Transplant. Proc. , 15 , 335 – 338 ( 1983. ). [Google Scholar]
  • 20).Lowry , R. P. , Gurley , K. E. , Blackburn , J. and Forbes , R. D. C.Delayed type hypersensitivity and lymphocytotoxicity in cardiac allograft rejection . Transplant. Proc. , 15 , 343 – 346 ( 1983. ). [Google Scholar]
  • 21).Tilney , N. L. , Kupiec‐Weglinshi , J. N. , Heidecke , C. D. , Lear , P. A. and Strom , T. B.Mechanisms of rejection and prolongation of vascularized organ aliografts . Immunol. Rev. , 77 , 185 – 216 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 22).Mason , D. W. and Morris , P. J.Effector mechanisms in allograft rejection . Ann, Rev. Immunol. , 4 , 119 – 145 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 23).LeFrancois , L. and Bevan , M. J.A reexamination of the role of Lyt‐2‐positive T cells in murine skin graft rejection . J. Exp. Med. , 159 , 57 – 67 ( 1984. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24).Fujiwara , H. , Yoshioka , T. , Shima , J. , Kosugi , A. , Itoh , K. and Hamaoka , T.Helper T cells against tumor‐associated antigens (TAA): preferential induction of helper T cell activities involved in anti‐TAA cytotoxic and antibody responses . J. Immunol. , 136 , 2715 – 2719 ( 1986. ). [PubMed] [Google Scholar]
  • 25).Kern , D. E. , Klarnet , J. P. , Jensen , M. C. V. and Greenberg , P. D.Requirement for recognition of class II molecules and processed tumor antigen for optimal generation of syngeneic tumor‐specific class I‐restricted CTL . J. Immunol. , 136 , 4303 – 4310 ( 1986. ). [PubMed] [Google Scholar]
  • 26).Kosugi , A. , Yoshioka , T. , Suda , T. , Sano , H. , Takahama , Y. , Fujiwara , H. and Hamaoka , T.The activation of L3T4 helper T cells assisting the generation of anti‐tumor Lyt‐2 cytotoxic T lymphocytes: requirement of lapositive antigen‐presenting cells for processing and presentation of tumor antigens . J. Leucocyte Biol. , 42 , 632 – 641 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 27).Yamamoto , H. , Takata , M. and Fujimoto , S.The role of L3T4‐positive T lymphocytes in the generation of antitumor immunity in the mouse . Jpn. J. Cancer Res. (Gann) , 78 , 176 – 184 ( 1987. ). [PubMed] [Google Scholar]
  • 28).Shimizu , Y. , Fujiwara , H. , Ueda , S. , Wakamiya , N. , Kato , S. and Hamaoka , T.The augmentation of tumor‐specific immunity by virus‐help. II. Enhanced induction of cytotoxic T lymphocyte and antibody responses to tumor antigens by vacciniareactive helper T cells . Eur. J. Immunol. , 14 , 839 – 843 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 29).Fujiwara , H. , Takai , Y. , Sakamoto , K. and Hamaoka , T.The mechanism of tumor growth inhibition by tumor‐specific Lyt‐l+2− T cells. I. Anti‐tumor effect of Lyt‐l+2− T cells depends on the existence of adherent cells . J. Immunol. , 135 , 2187 – 2191 ( 1985. ). [PubMed] [Google Scholar]
  • 30).Sakamoto , K. , Fujiwara , H. , Nakajima , H. , Yoshioka , T. , Takai , Y. and Hamaoka , T.The mechanism of tumor growth inhibition of tunor‐specific Lyt‐1+2− T cells. II. Requirements of adherent cells for activating Lyt‐1 +2− T cells as well as for functioning as antitumor effectors activated by factor (s) from Lyt‐1+2− T cells . Jpn. J. Cancer Res. (Gann) , 77 , 1142 – 1152 ( 1986. ). [PubMed] [Google Scholar]
  • 31).Nakajima , J. , Fujiwara , H. , Takai , Y. , Izumi , Y. , Sano , S. , Tsuchida , T. and Hamaoka , T.Studies on macrophage‐activating factor (MAF) in antitumor immune responses. I. Tumor specific Lyt‐1+2− T cells are required for producing MAF able to generate cytolytic as well as cytostatic macrophages . J. Immunol. , 135 , 2199 – 2205 ( 1985. ). [PubMed] [Google Scholar]
  • 32).Swain , S. L. and Panfili , P. R.Helper cells activated by allogeneic H‐2K or H‐2D differences have Ly phenotype distinct from those responsive to I differences . J. Immuno. , 122 , 383 – 391 ( 1979. ). [PubMed] [Google Scholar]
  • 33).Swain , S. L. , Bakke , A. , English , M. and Dutton , R. W.Ly phenotype and MHC recognition: the allohelper that recognizes K or D is a mature Lyl23 cell . J. Immunol. , 123 , 2716 – 2724 ( 1979. ). [PubMed] [Google Scholar]
  • 34).Mizuochi , T. , Golding , H. , Rosenberg , A. S. , Glimcher , L. H. , Malek , T. R. and Singer , A.Both L3T4+ and Lyt‐2+ helper T cells initiate cytotoxic T lymphocyte responses against allogeneic major histocompatibility antigens but not against trinitrophenyl‐modified self . J. Exp. Med. , 162 , 427 – 443 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35).Mizuochi , T. , Ono , S. , Malek , T. R. and Singer , A.Characterization of two distinct primary T cell populations that secrete interleukin 2 upon recognition of class I or class II major histocompatibility antigens . J. Exp. Med. , 163 , 603 – 619 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36).Greenberg , P. D.Effector mechanisms by which adoptively transferred T cells promote tumor eradication . In “ Cellular Immunotherapy of Cancer ”, ed. Gale R. P. , Truitt R. L. and Bortin M. M. ( 1987. ), in press . Alan R Liss Inc. , New York . [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES