Summary
We induced nonspecific killer cells in the local site of delayed-type hypersensitivity against keyhole limpet hemocyanin or ovalbumin. Delayed-type hypersensitivity was induced in the peritoneal cavities of mice, and peritoneal exudate cells (PEC) were collected. These PEC were found to have killer activity toward SP2 and YAC-1 cells (target cells susceptible to natural killer cells) by 4-h 51Cr-release assays. The induction of killer activity in PEC was observed in parallel with the eliciting of delayed-type hypersensitivity in the peritoneal cavity, in which the killer activity was maximum 24–48 h after the antigen challenge, but was not induced in nu/nu mice and was induced in an antigen-specific way. These killer cells did not adhere to nylon wool and had Thy1 and asialo-GM1 antigens on their surfaces. Their precursor cells were also asialo-GM1-positive. These findings indicate that the killer cells probably belong to the NK cell lineage. Results of tumor challenge experiments showed that these killer cells had an antitumor effect in vivo as well as in vitro.
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Akagawa KS, Tokunaga T (1982) Appearance of a cell surface antigen associated with the activation of peritoneal macrophages in mice. Microbiol Immunol 26:831
Akagawa KS, Maruyama Y, Takano M, Kasai M, Tokunaga T (1981) A cell surface antigen expressed on mouse lung macrophages. Microbiol Immunol 25:1215
Bartlett GL, Zbar B, Branch B (1972) Tumor-specific vaccine containing Mycobacterium bovis and tumor cells: safety and efficacy. J Natl Cancer Inst 48:1709
Brooks CG, Kuribayashi K, Sale GE, Henney CS (1982) Characterization of five cloned murine cell lines showing high cytolytic activity against YAC-1 cells. J Immunol 128:2326
Cantor H, Boyse EA (1975) Functional subclasses of T lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J Exp Med 141:1376
Cheever MA, Greenberg PD, Fefer A, Gillis S (1982) Augmentation of the anti-tumor therapeutic efficacy of long-term cultured T lymphocytes by in vivo administration of purified interleukin 2. J Exp Med 155:968
Djeu JY, Heinbaugh JA, Holden WT, Herberman RB (1979) Augmentation of mouse natural killer cell activity by interferon inducers. J Immunol 122:175
Fernandez-Cruz E, Woda BA, Feldman JD (1980) Elimination of syngeneic sarcomas in rats by a subset of T lymphocytes. J Exp Med 152:823
Fujiwara H, Fukuzawa M, Yoshioka T, Nakajima H, Hamaoka T (1984) The role of tumor-specific Lyt-1+2− T cells in eradicating tumor cells in vivo. I. Lyt-1+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
Greenberg PD (1986) Therapy of murine leukemia with cyclophosphamide and immune Lyt-2+ cells can mediate eradication of disseminated leukemia. J Immunol 136:1917
Greenberg PD, Cheever MA, Feffer A (1981) Eradication of disseminated murine leukemia by chemoimmunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt-1+2− lymphocytes. J Exp Med 154:952
Greenberg PD, Kern DE, Cheever MA (1985) Therapy of disseminated murine leukemia with cyclophosphamide and immune Lyt-1+2− T cells. Tumor eradication does not require participation of cytotoxic T cells. J Exp Med 161:1122
Habu S, Fukui H, Shimamura K, Kasai M, Nagai Y, Okumura K, Tamaoki N (1981) In vivo effect of anti-asialo GM1. I. Reduction of NK activity and enhancement of transplanted tumor growth in nude mice. J Immunol 127:34
Henney CS, Kuribayashi K, Kern DE, Gills S (1981) Interleukin-2 augments natural killer cell activity. Nature 291:335
Herberman RB, Nunn ME, Holden HT, Lavrin DH (1975) Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. II. Characterization of effector cells. Int J Cancer 16:230
Herberman RB, Nunn ME, Lavrin DH (1975) Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. I. Distribution of reactivity and specificity. Int J Cancer 16:216
Herberman RB, Nunn ME, Holden HT (1978) Low density of the Thy 1 antigen on mouse effector cells mediating natural cytotoxicity against tumor cells. J Immunol 121:304
Hollander N (1982) Effect of anti-Lyt antibodies on T-cell functions. Immunol Rev 68:45
Hurme M, Shivola M (1983) Natural killer (NK) cell activity during lymphatic regeneration: Early appearance of Thy-1+ NK cells and highly interleukin 2- (IL2) receptive, Thy-1− cells. J Immunol 131:658
Iwahashi T, Kuribayashi K, Takao T, Saito K (1986) The characteristics of the activated killer cells (AK) induced in vitro with recombinant IL-2 (rIL-2). Jpn J Allergol 35:1047
Julius MH, Simpson E, Herzenberg LA (1973) A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol 3:645
Kasai M, Leclerc JC, Shen FW, Cantor H (1979) Identification of Ly 5 on the surface of “natural killer” cells in normal and athymic inbred mouse strains. Immunogenetics 8:153
Kasai M, Iwamori M, Nagai Y, Okumura K, Tada T (1980) A glycolipid on the surface of mouse natural killer cells. Eur J Immunol 10:175
Kiessling R, Klein E, Pross H, Wigzell H (1975) “Natural” killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell. Eur J Immunol 5:117
Koo GC, Jacobson JB, Hammerling GJ, Hammerling U (1980) Antigenic profile of murine natural killer cells. J Immunol 125:1003
Mercrio AM, Schwarting GA, Robbins PW (1984) Glycolipids of the mouse peritoneal macrophage. Alterations in amount and surface exposure of specific glycolipid species occur in response to inflammation and tumoricidal activation. J Exp Med 160:1114
Minato N, Reid L, Cantor H, Lengyel P, Bloom BR (1980) Mode of regulation of natural killer cell activity by interferon. J Exp Med 152:124
Minato N, Reid L, Bloom B (1981) On the heterogeneity of murine natural killer cells. J Exp Med 154:750
Mitsuya H, Matis LA, Megson M, Bunn PA, Murray C, Mann DL, Gallo RC, Broder S (1983) Generation of an HLA restricted cytotoxic T cell line reactive against cultured tumor cells from a patient infected with human T cell leukemia/lymphoma virus. J Exp Med 158:994
Nakayama E, Shiku H, Stockert E, Oettgen HF, Old LJ (1979) Cytotoxic T cells: Lyt phenotype and blocking of killing activity by Lyt antisera. Proc Natl Acad Sci USA 76:1977
Rosenstein M, Yron I, Kaufmann Y, Rosenberg A (1983) Lymphokine-activated killer cells: lysis of fresh syngeneic natural killer-resistant murine tumor cells by lymphocyte cultured in interleukin 2. Cancer Res 44:1946
32.Suzuki R, Handa K, Itoh K, Kumagai K (1983) Natural killer (NK) cells as a responder to interleukin 2 (IL 2). I. Proliferative response and establishment of cloned cells. J Immunol 130:981
Ting CC, Yang SS (1982) Effect of interleukin 2 on cytotoxic effectors: I. Short-term culture of the cytotoxic effectors and the in vivo anti-tumor activity of the cultured effectors isolated from tumor site. Int J Cancer 30:625
Ting CC, Bluestone JA, Halgrove ME, Loh NN (1986) Expression and function of asialo GM1 in alloreactive cytotoxic T lymphocytes. J Immunol 137:2100
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Takao, T., Morikawa, Y., Kuribayashi, K. et al. Induction of nonspecific killer cells by delayed-type hypersensitivity against soluble protein antigens in murine peritoneal cavities. Cancer Immunol Immunother 29, 219–225 (1989). https://doi.org/10.1007/BF00199999
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DOI: https://doi.org/10.1007/BF00199999