Specific cytotoxicity against autologous tumour and proliferative responses of human lymphocytes grown in interleukin 2

International Journal of Cancer - Tập 29 Số 1 - Trang 33-39 - 1982
B. M. Vose1,2, Guy D. Bonnard1,2
1Laboratory for Immunodiagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20205
2Transplantation Research Branch, Naval Medical Research Institute and Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20014, USA

Tóm tắt

AbstractPeripheral blood lymphocytes of cancer patients were sensitized in vitro to autologous tumour cells in mixed lymphocyte‐tumour culture (MLTC). Blast cells were isolated on discontinuous Percoll gradients from MLTC which showed significant stimulation of [<3>H]‐thymidine incorporation. Cultured T cells (CTC) were derived from these blasts by growth in conditioned medium containing interteukin‐2 (IL‐2) and maintained for up to 51 days by repeated feeding with IL‐2 and in some cases by addition of irradiated allogeneic blood mononuclear cells as “fillers”. These cultures showed specific cytotoxic reactivity against autologous tumour and in only a few cases was natural killing (NK) of K562 cells apparent. Restimulation of CTC with tumour was measured in primed lymphocyte tests (PLT). Increased uptake of [<3>H]‐thymidine was found upon stimulation by autologous tumour and allogeneic tumour of the same site and histology but there was no response to non‐related tumours or to a panel of allogeneic lymphocytes. No sensitization to autologous HLA D/DR could be detected by restimulation or cytotoxicity against monocytes in the majority of cases. These data suggest that, by careful selection of sensitised blasts from MLTC, it is possible to obtain CTC with both helper (proliferative) and cytotoxic T cells and that such CTC have specific reactivity against tumour cells. These cellular reagents will be useful in defining the antigenicity of human neoplasms and possibly in therapy.

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Tài liệu tham khảo

Alvarez J. M., 1978, Cytotoxic activities of normal cultured human T cells, J. Immunol., 121, 1270, 10.4049/jimmunol.121.4.1270

10.1038/281307a0

10.1126/science.180.4084.403

Bonnard G. D., 1981, The lymphocyte, 45

Bonnard G. D., 1978, Human lymphocyte Differentiation: its application to cancer, 319

10.1016/0008-8749(80)90270-1

Cheever M. A., 1981, Specific adoptive therapy of established leukaemia with syngeneic lymphocytes sequentially immunised in vivo and in vitro and non‐specifically expanded by culture with interleukin‐2, J. Immunol., 126, 1318, 10.4049/jimmunol.126.4.1318

Cochran A. J., 1973, Cellular immunity to breast cancer and malignant melanoma, Brit. J. Cancer, 28, 77, 10.1038/bjc.1973.79

Csako G., 1980, Cloning of human lymphocytes reactive with autologous leukaemia cells, Cancer Res., 40, 3218

Eckels D. D. andHartzman R. J. Evidence for a T‐lymphocyte clone (TLC) restimulating determinant encoded by a new gene linked to HLA.Human Immunol.(1981) in press.

10.1002/ijc.2910070102

Kedar E. Ikerui B. Timonen T. Bonnard G. D. andHerberman R. B. Cytotoxicity of human cultured T cells against tumour target cell lines. Submitted (1981).

10.1084/jem.143.5.1042

Kurnick J. T., 1979, Long‐term growth in vitro of human T cell blasts with maintenance of specificity and function, J. Immunol., 122, 1255, 10.4049/jimmunol.122.4.1255

Lotze M. T. Grimm E. A. Mazumder A. Strausser J. L. andRosenberg S. A. In vitrogrowth of cytotoxic human lymphocytes. IV. Lysis of fresh and cultured autologous tumour by lymphocytes cultured in T cell growth factor (TCGF).Cancer Research in press (1981).

Lotze M. T., 1981, In vitro growth of cytotoxic human lymphocytes. III. The preparation of lectin‐free T cell growth factor (TCGF) and an analysis of its activity, J. Immunol., 126, 2215, 10.4049/jimmunol.126.6.2215

Ortaldo J. R., 1980, Natural killing and antibody‐dependent cell‐mediated cytotoxicity by human cultured T cells, Behring Inst. Mitt., 67, 258

Reinsmoen N. L., 1978, Antigens associated with acute leukaemia detected in the primed lymphocyte test, J. nat. Cancer Inst., 60, 537, 10.1093/jnci/60.3.537

10.1111/j.1365-3083.1980.tb00214.x

Schendel D. J., 1980, Proliferative and cytotoxic human cultured T‐cell lines specific for major histocompatibility complex (MHC) antigens, Behring Inst. Mitt., 67, 252

10.1126/science.124948

Slease R. B., Clinical effects of infusions into chimpanzees of autologous cultured T cells (CTC) primed in mixed lymphocyte culture, J. nat. Cancer Inst., 67, 489

Sondel P. M., 1976, Cell‐mediated destruction of human leukemic cells by MHC identical lymphocytes: requirement for a proliferative trigger in vitro, J. Immunol., 117, 2197, 10.4049/jimmunol.117.6.2197

10.1002/ijc.2910280205

Timonen T. Ortaldo J. R. Stadler B. M. Bonnard G. D. andHerberman R. B. Cultures of purified human natural killer cells: growth in the presence of Interleukin‐2. Submitted for publication (1981).

10.1016/0022-1759(80)90133-7

Troye M., 1977, The use of Fab fragments of anti‐human immunoglobulin as analytic tools for establishing the involvement of immunoglobulin in the spontaneous cytotoxicity to cultured tumour cells by lymphocytes from patients with bladder carcinoma and from healthy donors, J. Immunol., 119, 1061, 10.4049/jimmunol.119.3.1061

Tsoukas C. D., 1981, T lymphocyte‐mediated cytotoxicity against autologous EBV‐genome bearing B cells, J. Immunol., 126, 1742, 10.4049/jimmunol.126.5.1742

Vanky F. T., 1979, Immunodiagnosis of cancer, Part 2, 998

Vanky F. T., 1979, Human tumour‐lymphocyte interaction in vitro. VI. Specificity of primary and secondary autologous lymphocyte‐mediated cytotoxicity, J. nat. Cancer Inst., 62, 1407

10.1016/0008-8749(80)90132-X

Vose B. M., 1981, Methodological surveys

Vose B. M. andBonnard G. D. Limiting dilution analysis of growth of human T cells and large granular lymphocytes in Interleukin‐2 (In preparation)1981.

10.1002/ijc.2910240510

10.1007/BF00205621

10.1016/0165-2478(81)90081-X

10.1002/ijc.2910210508

10.1002/ijc.2910200407

10.1038/280685a0