Abstract
In vivo administrations of anti‐Lyt‐2.2 (CDS) mAb and anti‐L3T4 (CD4) mAb selectively eliminated CD8+ cells amd CD4+ cells, respectively. The relative potencies of CD8+ cells and CD4+ cells and their roles in primary tumor rejections were studied by investigating the effects of these mAbs on tumor growth. CD8+ cells were themselves fully capable of mediating rejection in 5 different tumor rejection systems: two radiation leukemia virus (RadLV)‐induced leukemias, B6RV2 and BALBRVD, a radiation‐induced leukemia BALBRL♂1, and a plasmacytoma BALBMOPC‐70A in CB6F1 mice, and a Friend virus‐induced leukemia B6FBL‐3 in B6 mice. On the other hand, CD4+ cells were capable of resisting tumor growth of B6FBL‐3, but not of the other four tumors. Furthermore, for efficient rejection of CB6F1UV+˚l sarcoma by CB6F1 mice, synergy of CDS+ and CD4+ cells was necessary. Blocking of UV+˚ 1 rejection was abrogated by delayed administration of anti‐L3T4 (CD4) mAb but not anti‐Lyt‐2.2 (CDS) mAb, indicating the involvement of CD4+ cells in only the initial phase of rejection.
Keywords: T‐cell subsets, Tumor rejection
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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. ) 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]
- 4. ) 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]
- 5. ) Eberlein , T. J. , Rosenstein , M. and Rosenberg , S. A.Regression of a disseminated syngeneic solid tumor by systemic transfer of lymphoid cells expanded in interleukin 2 . J. Exp. Med. , 156 , 385 – 397 ( 1982. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. ) Engers , H. D. , Lahaye , T. , Sorenson , G. D. , Glasebrook , A. L. , Horvath , C. and Brunner , K. T.Functional activity in vivo of effector T cell populations. II. Anti‐tumor activity exhibited by syngeneic anti‐MoMuLV‐specific cytolytic T cell clones . J. Immunol , 133 , 1664 – 1670 ( 1984. ). [PubMed] [Google Scholar]
- 7. ) 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]
- 8. ) Greenberg , P. D. , Cheever , M. A. and Fefer , A.Eradication of disseminated murine leukemia by chemoimmuno‐therapy 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]
- 9. ) Nakayama , E. , Uenaka , A. , Stockert , E. and Obata , Y.Detection of a unique antigen on radiation leukemia virus‐induced leukemia B6RV2 . Cancer Res. , 44 , 5138 – 5144 ( 1984. ). [PubMed] [Google Scholar]
- 10. ) Sato , H. , Boyse , E. A. , Aoki , T. , Iritani , C. and Old , L. J.Leukemia‐associated transplantation antigens related to murine leukemia virus. The X. 1 system: immune response controlled by a locus linked to H‐2 . J. Exp. Med. , 138 , 593 – 606 ( 1973. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. ) Matis , L. A. , Ruscetti , S. K. , Longo , D. L. , Jacobson , S. , Brown , E. J. , Zinn , S. and Kruisbeek , A. M.Distinct proliferative T cell clonotypes are generated in response to a murine retrovirus‐induced syngeneic T cell leukemia: viral gp70 antigen‐specific MT4+ clones and Lyt‐2+ cytolytic clones which recognize a tumor‐specific cell surface antigen . J. Immunol , 135 , 703 – 713 ( 1985. ). [PubMed] [Google Scholar]
- 12. ) Kuribayashi , K. , Tanaka , C. , Matsubayashi , Y. , Masuda , T. , Udono , H. , Abe , M. , Nakayama , E. and Shiku , H.Anti‐idiotypic antibodies against UV‐induced tumor‐specific CTL clones: preparation in syngeneic combination . J. Immunol , 141 , 4047 – 4080 ( 1988. ). [PubMed] [Google Scholar]
- 13. ) Nakayama , E. and Uenaka , A.Effect of in vivo administration of Lyt antibodies. Lyt phenotype of T cells in lymphoid tissues and blocking of tumor rejection . J. Exp. Med. , 161 , 345 – 355 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. ) 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 GK1.5: similarity of L3T4 to the human Leu‐3/T4 molecule . J. Immunol , 131 , 2445 – 2451 ( 1983. ). [PubMed] [Google Scholar]
- 15. ) Ichikawa , T. , Nakayama , E. , Uenaka , A. , Monden , M. and Mori , T.Effector cells in allelic H‐2 class I‐incompatible skin graft rejection . J. Exp. Med. , 166 , 982 – 990 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. ) Rosenberg , A. S. , Mizuochi , T. , Sharrow , S. and Singer , A.Phenotype, specificity, and function of T cell subsets and T cell interactions involved in skin allograft rejection . J. Exp. Med. , 165 , 1296 – 1315 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. ) Morishita , H. , Shiku , H. , Horibe , K. , Obata , Y. , Stockert , E. , Oettgen , H. F. , Old , L. J. and Yamada , K.Cell surface antigens of murine leukemias induced by radiation leukemia virus. Recognition of individually distinct cell surface antigens by cytotoxic T cells on leukemias expressing crossreactive transplantation antigens . J. Exp. Med. , 163 , 452 – 457 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. ) Kaneko , Y. , Natsuume‐Sakai , S. , Moriwaki , K. and Migita , S. F.hybrid resistance to murine plasmacytoma MOPC‐70A: hybrid resistance to MOPC‐70A controlled by a locus linked to H‐2 . J Immunol , 125 , 2031 – 2038 ( 1980. ). [PubMed] [Google Scholar]
- 19. ) Nakayama , E. , Shiku , H. , Takahashi , T. , Oettgen , H. F. and Old , L. J.Definition of a unique cell surface antigen of mouse leukemia RL♂1 by cell‐mediated cytotoxicity . Proc. Natl. Acad. Sci. USA , 76 , 3486 – 3490 ( 1979. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. ) Kripke , M. L.Antigenicity of murine skin tumors induced by ultraviolet light . J. Natl. Cancer Inst. , 53 , 1333 – 1336 ( 1974. ). [DOI] [PubMed] [Google Scholar]
- 21. ) Stauss , H. J. , van vanWaes , C. , Fink , M. A. , Starr , B. and Schreiber , H.Indentification of a unique tumor antigen as rejection antigen by molecular cloning and gene transfer . J. Exp. Med. , 164 , 1516 – 1530 ( 1983. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. ) Klarnet , J. P. , Kern , D. E. , Okuno , K. , Holt , C.Lilly , F. and Greenberg , P. D.FBL‐reactive CD8+ cytotoxic and CD4+ helper T lymphocytes recognize distinct Friend murine leukemia virus‐encoded antigens . J. Exp, Med. , 169 , 457 – 467 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. ) Bateman , W. J. , Jenkinson , E. J. and Owen , J. J. T.T‐Cell immunity to murine Moloney sarcoma virus‐induced tumours: L3T4+ T cells are necessary for resistance to primary sarcoma growth, but Lyt‐2+ T cells are required for resistance to secondary tumour cell challenge . Immunology , 61 , 317 – 320 ( 1987. ). [PMC free article] [PubMed] [Google Scholar]