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. 1979 Sep 19;150(3):531–547. doi: 10.1084/jem.150.3.531

Hybrid resistance to EL-4 lymphoma cells. I. Characterization of natural killer cells that lyse EL-4 cells and their distinction from marrow-dependent natural killer cells

PMCID: PMC2185646  PMID: 383877

Abstract

Natural killer (NK) cells from nonimmunized mice capable of lysing EL-4 (C57BL/6 strain H-2b) tissue culture-adapted lymphoma cells have been analyzed and compared with NK cells which lyse YAC-1 (A-strain, H-2a) lymphoma cells. A correlation was seen in the ability of inbred and B6D2F1 mice to reject C57BL/6 (B6) bone-marrow grafts and the ability of their spleen cells to lyse EL-4 cells in vitro. This suggests that hybrid or hemopoietic histocompatibility antigens, (Hh-1b), relevant in the rejection of B6 stem cells may also be the relevant target structures for the anti-EL-4 NK cells. Certain features of these NK cells are similar to the NK cells reactive against YAC-1 cells. Both types of NK cells are present in athymic nude mice, are not affected by treatment with anti-immunoglobulin plus complement, and are not depleted by techniques that remove macrophages. NK activity against both targets is stimulated 3 d after injection of Corynebacterium parvum, and 24 h after challenge with polyinosinic:polycytidylic acid. Hydrocortisone acetate and cyclophosphamide lead to reduction of NK activity within 2-3 d after administration. However, the anti-YAC and anti-EL-4 NK reactivities differed in several important respects. Treatment of mice with 89Sr, the bone-seeking isotope, to deplete marrow-dependent cells, depleted the anti-YAC-1 but not anti-EL-4 cell functions. Anti-EL-4 NK cells were unaffected by silica particles in vivo or in vitro; the NK cells reactive to EL-4 cells matured functionally much earlier in life (5 d of age) and the function did not decline with age. Irradiated mice reconstituted with syngeneic marrow or spleen cells developed functional NK cells against EL-4 targets before they developed anti-YAC-1 NK cells in their spleen. Thus anti-EL- 4 NK cells that express hybrid resistance in vitro appear to differ from anti-YAC-1 NK cells and do not require an intact marrow microenvironment for functional differentiation. Despite differences in the NK-cell types involved in the lysis of YAC-1 and EL-4 cells, these two tumor cells share certain common determinants. This was ascertained both by cold competition and by utilization of YAC-1 and EL-4 cell monolayers as immunoadsorbents. We conclude that Hh-1b is the common antigen present in EL-4 and YAC-1 cells, because B6D2F1 anti-B6 (anti- Hh-1b) cytotoxic T lymphocytes lysed both the tumor cells. Our data suggest that Hh-1b antigen is recognized by both types of NK cells, but that additional determinants must be present on YAC-1 cells. Two models of NK cell lysis compatible with the data are presented.

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Selected References

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

  1. Bennett M., Baker E. E., Eastcott J. W., Kumar V., Yonkosky D. Selective elimination of marrow precursors with the bone-seeking isotope 89Sr: implications for hemopoiesis, lymphopoiesis, viral leukemogenesis and infection. J Reticuloendothel Soc. 1976 Jul;20(1):71–87. [PubMed] [Google Scholar]
  2. Bennett M., Baker E. E. Marrow-dependent cell function in early stages of infection with Listeria monocytogenes. Cell Immunol. 1977 Sep;33(1):203–210. doi: 10.1016/0008-8749(77)90147-2. [DOI] [PubMed] [Google Scholar]
  3. Bennett M., Pinkerton P. H., Cudkowicz G., Bannerman R. M. Hemopoietic progenitor cells in marrow and spleen of mice with hereditary iron deficiency anemia. Blood. 1968 Dec;32(6):908–921. [PubMed] [Google Scholar]
  4. Bennett M. Prevention of marrow allograft rejection with radioactive strontium: evidence for marrow-dependent effector cells. J Immunol. 1973 Feb;110(2):510–516. [PubMed] [Google Scholar]
  5. Campbell P. A., Martens B. L., Cooper H. R., McClatchy J. K. Requirement for bone marrow-derived cells in resistance to Listeria. J Immunol. 1974 Apr;112(4):1407–1414. [PubMed] [Google Scholar]
  6. Cudkowicz G., Bennett M. Peculiar immunobiology of bone marrow allografts. I. Graft rejection by irradiated responder mice. J Exp Med. 1971 Jul 1;134(1):83–102. doi: 10.1084/jem.134.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cudkowicz G., Bennett M. Peculiar immunobiology of bone marrow allografts. II. Rejection of parental grafts by resistant F 1 hybrid mice. J Exp Med. 1971 Dec 1;134(6):1513–1528. doi: 10.1084/jem.134.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cudkowicz G. Genetic control of bone marrow graft rejection. I. Determinant-specific difference of reactivity in two pairs of inbred mouse strains. J Exp Med. 1971 Jul 1;134(1):281–293. doi: 10.1084/jem.134.1.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cudkowicz G., Lotzová E. Hemopoietic cell-defined components of the major histocompatibility complex of mice: identification of responsive and unresponsive recipients for bone marrow transplants. Transplant Proc. 1973 Dec;5(4):1399–1405. [PubMed] [Google Scholar]
  10. Haller O., Wigzell H. Suppression of natural killer cell activity with radioactive strontium: effector cells are marrow dependent. J Immunol. 1977 Apr;118(4):1503–1506. [PubMed] [Google Scholar]
  11. Herberman R. B., Bartram S., Haskill J. S., Nunn M., Holden H. T., West W. H. Fc receptors on mouse effector cells mediating natural cytotoxicity against tumor cells. J Immunol. 1977 Jul;119(1):322–326. [PubMed] [Google Scholar]
  12. Herberman R. B., Nunn M. E., Holden H. T., Lavrin D. H. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. II. Characterization of effector cells. Int J Cancer. 1975 Aug 15;16(2):230–239. doi: 10.1002/ijc.2910160205. [DOI] [PubMed] [Google Scholar]
  13. Herberman R. B., Nunn M. E., Holden H. T. Low density of Thy 1 antigen on mouse effector cells mediating natural cytotoxicity against tumor cells. J Immunol. 1978 Jul;121(1):304–309. [PubMed] [Google Scholar]
  14. Kiessling R., Hochman P. S., Haller O., Shearer G. M., Wigzell H., Cudkowicz G. Evidence for a similar or common mechanism for natural killer cell activity and resistance to hemopoietic grafts. Eur J Immunol. 1977 Sep;7(9):655–663. doi: 10.1002/eji.1830070915. [DOI] [PubMed] [Google Scholar]
  15. Kiessling R., Klein E., Pross H., Wigzell H. "Natural" killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell. Eur J Immunol. 1975 Feb;5(2):117–121. doi: 10.1002/eji.1830050209. [DOI] [PubMed] [Google Scholar]
  16. Kumar V., Bennett M., Eckner R. J. Mechanisms of genetic resistance to friend virus leukemia in mice. J Exp Med. 1974 May 1;139(5):1093–1109. doi: 10.1084/jem.139.5.1093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kumar V., Bennett M. Mechanisms of genetic resistance to Friend virus leukemia in mice. II. Resistance of mitogen-responsive lymphocytes mediated by marrow-dependent cells. J Exp Med. 1976 Apr 1;143(4):713–727. doi: 10.1084/jem.143.4.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kumar V., Caruso T., Bennett M. Mechanisms of genetic resistance to Friend virus leukemia. III. Susceptibility of mitogen-responsive lymphocytes mediated by T cells. J Exp Med. 1976 Apr 1;143(4):728–740. doi: 10.1084/jem.143.4.728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kumar V., Goldschmidt L., Eastcott J. W., Bennett M. Mechanisms of genetic resistance to Friend virus leukemia in mice. IV. Identification of a gene (Fv-3) regulating immunosuppression in vitro, and its distinction from Fv-2 and genes regulating marrow allograft reactivity. J Exp Med. 1978 Feb 1;147(2):422–433. doi: 10.1084/jem.147.2.422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lindahl F., Peck A. B., Bach F. H. Specificity of cell-mediated lympholysis for public and private H-2 determinants. Scand J Immunol. 1975 Sep;4(5-6):541–553. doi: 10.1111/j.1365-3083.1975.tb02660.x. [DOI] [PubMed] [Google Scholar]
  21. Ly I. A., Mishell R. I. Separation of mouse spleen cells by passage through columns of sephadex G-10. J Immunol Methods. 1974 Aug;5(3):239–247. doi: 10.1016/0022-1759(74)90108-2. [DOI] [PubMed] [Google Scholar]
  22. Martin W. J. Immune surveillance directed against depressed cellular and viral alloantigens. Cell Immunol. 1975 Jan;15(1):1–10. doi: 10.1016/0008-8749(75)90159-8. [DOI] [PubMed] [Google Scholar]
  23. Merluzzi V. J., Levy E. M., Kumar V., Bennett M., Cooperband S. R. In vitro activation of suppressor cells from spleens of mice treated with radioactive strontium. J Immunol. 1978 Aug;121(2):505–512. [PubMed] [Google Scholar]
  24. Roder J. C., Kiessling R., Biberfeld P., Andersson B. Target-effector interaction in the natural killer (NK) cell system. II. The isolation of NK cells and studies on the mechanism of killing. J Immunol. 1978 Dec;121(6):2509–2517. [PubMed] [Google Scholar]
  25. Shearer G. M., Cudkowicz G. Induction of F1 hybrid antiparent cytotoxic effector cells: an in vitro model for hemopoietic histoincompatibility. Science. 1975 Nov 28;190(4217):890–893. doi: 10.1126/science.1188368. [DOI] [PubMed] [Google Scholar]
  26. Shearer G. M., Cudkowicz G., Schmitt-Verhulst A. M., Rehn T. G., Waksal H., Evans P. D. F1 hybrid antiparental cell-mediated lympholysis: a comparison with bone marrow graft rejection and with cell-mediated lympholysis to alloantigens. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):511–518. doi: 10.1101/sqb.1977.041.01.059. [DOI] [PubMed] [Google Scholar]
  27. Stulting R. D., Berke G. Nature of lymphocyte-tumor interaction. A general method for cellular immunoabsorption. J Exp Med. 1973 Apr 1;137(4):932–942. doi: 10.1084/jem.137.4.932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Welsh R. M., Jr Cytotoxic cells induced during lymphocytic choriomeningitis virus infection of mice. I. Characterization of natural killer cell induction. J Exp Med. 1978 Jul 1;148(1):163–181. doi: 10.1084/jem.148.1.163. [DOI] [PMC free article] [PubMed] [Google Scholar]

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