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. 1983 Mar 1;157(3):843–861. doi: 10.1084/jem.157.3.843

Cloned mouse cells with natural killer function and cloned suppressor T cells express ultrastructural and biochemical features not shared by cloned inducer T cells

PMCID: PMC2186969  PMID: 6220105

Abstract

We have examined the morphology, cytochemistry, and biochemistry of mouse leukocyte subsets by analyzing cloned leukocyte populations specialized to perform different immunologic functions. Cloned cells expressing high-affinity plasma membrane receptors for IgE and mediating natural killer (NK) lysis and cloned antigen-specific suppressor T cells contained prominent osmiophilic cytoplasmic granules similar by ultrastructure to those of mouse basophils. Both clones also incorporated 35SO4 into granule-associated sulfated glycosaminoglycans, expressed a characteristic ultrastructural pattern of nonspecific esterase activity, incorporated exogenous [3H]5-hydroxytryptamine, and contained cytoplasmic deposits of particulate glycogen. By contrast, cloned inducer T cells lacked cytoplasmic granules and glycogen, incorporated neither 35SO4 nor [3H]5-hydroxytryptamine, and differed from the other clones in pattern of nonspecific esterase activity. These findings establish that certain cloned cells with NK activity and cloned suppressor T cells express morphologic and biochemical characteristics heretofore associated with basophilic granulocytes. However, these clones differ in surface glycoprotein expression and immunologic function, and the full extent of the similarities and differences among these populations and basophils remains to be determined.

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Selected References

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  1. BITTER T., MUIR H. M. A modified uronic acid carbazole reaction. Anal Biochem. 1962 Oct;4:330–334. doi: 10.1016/0003-2697(62)90095-7. [DOI] [PubMed] [Google Scholar]
  2. Bozdech M. J., Bainton D. F. Identification of alpha-naphthyl butyrate esterase as a plasma membrane ectoenzyme of monocytes and as a discrete intracellular membrane-bounded organelle in lymphocytes. J Exp Med. 1981 Jan 1;153(1):182–195. doi: 10.1084/jem.153.1.182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brooks C. G., Kuribayashi K., Sale G. E., Henney C. S. Characterization of five cloned murine cell lines showing high cytolytic activity against YAC-1 cells. J Immunol. 1982 May;128(5):2326–2335. [PubMed] [Google Scholar]
  4. Bykovskaja S. N., Rytenko A. N., Rauschenbach M. O., Bykovsky A. F. Ultrastructural alteration of cytolytic T lymphocytes following their interaction with target cells. I. Hypertrophy and change of orientation of the Golgi apparatus. Cell Immunol. 1978 Sep 15;40(1):164–174. doi: 10.1016/0008-8749(78)90324-6. [DOI] [PubMed] [Google Scholar]
  5. Bykovskaja S. N., Rytenko A. N., Rauschenbach M. O., Bykovsky A. F. Ultrastructural alteration of cytolytic T lymphocytes following their interaction with target cells. II. Morphogenesis of secretory granules and intracellular vacuoles. Cell Immunol. 1978 Sep 15;40(1):175–185. doi: 10.1016/0008-8749(78)90325-8. [DOI] [PubMed] [Google Scholar]
  6. Carpen O., Virtanen I., Saksela E. Ultrastructure of human natural killer cells: nature of the cytolytic contacts in relation to cellular secretion. J Immunol. 1982 Jun;128(6):2691–2697. [PubMed] [Google Scholar]
  7. Carpén O., Virtanen I., Saksela E. The cytotoxic activity of human natural killer cells requires an intact secretory apparatus. Cell Immunol. 1981 Feb;58(1):97–106. doi: 10.1016/0008-8749(81)90152-0. [DOI] [PubMed] [Google Scholar]
  8. Clark S. L., Jr Incorporation of sulfate by the mouse thymus: its relation to secretion by medullary epithelial cells and to thymic lymphopoiesis. J Exp Med. 1968 Nov 1;128(5):927–957. doi: 10.1084/jem.128.5.927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dean M. F., Muir H. The characterization of a protein-polysaccharide isolated from Kurloff cells of the guinea pig. Biochem J. 1970 Aug;118(5):783–790. doi: 10.1042/bj1180783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dvorak A. M., Galli S. J., Morgan E., Galli A. S., Hammond M. E., Dvorak H. F. Anaphylactic degranulation of guinea pig basophilic leukocytes. I. Fusion of granule membranes and cytoplasmic vesicles formation and resolution of degranulation sacs. Lab Invest. 1981 Feb;44(2):174–191. [PubMed] [Google Scholar]
  11. Dvorak A. M., Galli S. J., Morgan E., Galli A. S., Hammond M. E., Dvorak H. F. Anaphylactic degranulation of guinea pig basophilic leukocytes. II. Evidence for regranulation of mature basophils during recovery from degranulation in vitro. Lab Invest. 1982 May;46(5):461–475. [PubMed] [Google Scholar]
  12. Dvorak A. M., Hammond M. E., Morgan E., Orenstein N. S., Galli S. J., Dvorak H. F. Evidence for a vesicular transport mechanism in guinea pig basophilic leukocytes. Lab Invest. 1980 Feb;42(2):263–276. [PubMed] [Google Scholar]
  13. Dvorak A. M., Monahan R. A., Dickersin G. R. Diagnostic electron microscopy. I. Hematology: differential diagnosis of acute lymphoblastic and acute myeloblastic leukemia. Use of ultrastructural peroxidase cytochemistry and routine electron microscopic technology. Pathol Annu. 1981;16(Pt 1):101–137. [PubMed] [Google Scholar]
  14. Dvorak A. M., Nabel G., Pyne K., Cantor H., Dvorak H. F., Galli S. J. Ultrastructural identification of the mouse basophil. Blood. 1982 Jun;59(6):1279–1285. [PubMed] [Google Scholar]
  15. Fresno M., McVay-Boudreau L., Nabel G., Cantor H. Antigen-specific T lymphocyte clones. II. Purification and biological characterization of an antigen-specific suppressive protein synthesized by cloned T cells. J Exp Med. 1981 May 1;153(5):1260–1274. doi: 10.1084/jem.153.5.1260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fresno M., Nabel G., McVay-Boudreau L., Furthmayer H., Cantor H. Antigen-specific T lymphocyte clones. I. Characterization of a T lymphocyte clone expressing antigen-specific suppressive activity. J Exp Med. 1981 May 1;153(5):1246–1259. doi: 10.1084/jem.153.5.1246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Galli S. J., Dvorak A. M., Ishizaka T., Nabel G., Der Simonian H., Cantor H., Dvorak H. F. A cloned cell with NK function resembles basophils by ultrastructure and expresses IgE receptors. Nature. 1982 Jul 15;298(5871):288–290. doi: 10.1038/298288a0. [DOI] [PubMed] [Google Scholar]
  18. Galli S. J., Dvorak A. M., Marcum J. A., Ishizaka T., Nabel G., Der Simonian H., Pyne K., Goldin J. M., Rosenberg R. D., Cantor H. Mast cell clones: a model for the analysis of cellular maturation. J Cell Biol. 1982 Nov;95(2 Pt 1):435–444. doi: 10.1083/jcb.95.2.435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gershon M. D., Altman R. F. An analysis of the uptake of 5-hydroxytryptamine by the myenteric plexus of the small intestine of the guinea pig. J Pharmacol Exp Ther. 1971 Oct;179(1):29–41. [PubMed] [Google Scholar]
  20. Grossi C. E., Cadoni A., Zicca A., Leprini A., Ferrarini M. Large granular lymphocytes in human peripheral blood: ultrastructural and cytochemical characterization of the granules. Blood. 1982 Feb;59(2):277–283. [PubMed] [Google Scholar]
  21. Hackett C. J., Sullivan K., Lin Y. L. Ultrastructure of an influenza virus-specific cytotoxic T-cell clone and its interaction with P815 and macrophage targets. Cell Immunol. 1982 Apr;68(2):276–286. doi: 10.1016/0008-8749(82)90112-5. [DOI] [PubMed] [Google Scholar]
  22. Kedar E., Ikejiri B. L., Sredni B., Bonavida B., Herberman R. B. Propagation of mouse cytotoxic clones with characteristics of natural killer (NK) cells. Cell Immunol. 1982 May 15;69(2):305–329. doi: 10.1016/0008-8749(82)90075-2. [DOI] [PubMed] [Google Scholar]
  23. Luini W., Boraschi D., Alberti S., Aleotti A., Tagliabue A. Morphological characterization of a cell population responsible for natural killer activity. Immunology. 1981 Aug;43(4):663–668. [PMC free article] [PubMed] [Google Scholar]
  24. Mazingue C., Dessaint J. P., Capron A. [3H]serotonin release: an improved method to measure mast cell degranulation. J Immunol Methods. 1978;21(1-2):65–77. doi: 10.1016/0022-1759(78)90224-7. [DOI] [PubMed] [Google Scholar]
  25. Metcalfe D. D., Lewis R. A., Silbert J. E., Rosenberg R. D., Wasserman S. I., Austen K. F. Isolation and characterization of heparin from human lung. J Clin Invest. 1979 Dec;64(6):1537–1543. doi: 10.1172/JCI109613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Monahan R. A., Dvorak H. F., Dvorak A. M. Ultrastructural localization of nonspecific esterase activity in guinea pig and human monocytes, macrophages, and lymphocytes. Blood. 1981 Dec;58(6):1089–1099. [PubMed] [Google Scholar]
  27. Nabel G., Allard W. J., Cantor H. A cloned cell line mediating natural killer cell function inhibits immunoglobulin secretion. J Exp Med. 1982 Aug 1;156(2):658–663. doi: 10.1084/jem.156.2.658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Nabel G., Bucalo L. R., Allard J., Wigzell H., Cantor H. Multiple activities of a cloned cell line mediating natural killer cell function. J Exp Med. 1981 Jun 1;153(6):1582–1591. doi: 10.1084/jem.153.6.1582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nabel G., Fresno M., Chessman A., Cantor H. Use of cloned populations of mouse lymphocytes to analyze cellular differentiation. Cell. 1981 Jan;23(1):19–28. doi: 10.1016/0092-8674(81)90266-x. [DOI] [PubMed] [Google Scholar]
  30. Nabel G., Galli S. J., Dvorak A. M., Dvorak H. F., Cantor H. Inducer T lymphocytes synthesize a factor that stimulates proliferation of cloned mast cells. Nature. 1981 May 28;291(5813):332–334. doi: 10.1038/291332a0. [DOI] [PubMed] [Google Scholar]
  31. Nabel G., Greenberger J. S., Sakakeeny M. A., Cantor H. Multiple biologic activities of a cloned inducer T-cell population. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1157–1161. doi: 10.1073/pnas.78.2.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nunez E. A., Gershon M. D. Species differences in mast cells of the thyroid gland. Endocrinology. 1973 Jan;92(1):152–159. doi: 10.1210/endo-92-1-152. [DOI] [PubMed] [Google Scholar]
  33. Ogren S., Lindahl U. Degradation of heparin in mouse mastocytoma tissue. Biochem J. 1971 Dec;125(4):1119–1129. doi: 10.1042/bj1251119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Orenstein N. S., Galli S. J., Dvorak A. M., Silbert J. E., Dvorak H. F. Sulfated glycosaminoglycans of guinea pig basophilic leukocytes. J Immunol. 1978 Aug;121(2):586–592. [PubMed] [Google Scholar]
  35. Quan P. C., Ishizaka T., Bloom B. R. Studies on the mechanism of NK cell lysis. J Immunol. 1982 Apr;128(4):1786–1791. [PubMed] [Google Scholar]
  36. Reynolds C. W., Timonen T., Herberman R. B. Natural killer (NK) cell activity in the rat. I. Isolation and characterization of the effector cells. J Immunol. 1981 Jul;127(1):282–287. [PubMed] [Google Scholar]
  37. Roder J. C., Argov S., Klein M., Petersson C., Kiessling R., Andersson K., Hansson M. Target-effector cell interaction in the natural killer cell system. V. Energy requirements, membrane integrity, and the possible involvement of lysosomal enzymes. Immunology. 1980 May;40(1):107–116. [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. Roder J. C., Lohmann-Matthes M. L., Domzig W., Wigzell H. The beige mutation in the mouse. II. Selectivity of the natural killer (NK) cell defect. J Immunol. 1979 Nov;123(5):2174–2181. [PubMed] [Google Scholar]
  40. Roder J. C. The beige mutation in the mouse. I. A stem cell predetermined impairment in natural killer cell function. J Immunol. 1979 Nov;123(5):2168–2173. [PubMed] [Google Scholar]
  41. Roder J., Duwe A. The beige mutation in the mouse selectively impairs natural killer cell function. Nature. 1979 Mar 29;278(5703):451–453. doi: 10.1038/278451a0. [DOI] [PubMed] [Google Scholar]
  42. Saito H., Yamagata T., Suzuki S. Enzymatic methods for the determination of small quantities of isomeric chondroitin sulfates. J Biol Chem. 1968 Apr 10;243(7):1536–1542. [PubMed] [Google Scholar]
  43. Saxena R. K., Saxena Q. B., Adler W. H. Defective T-cell response in beige mutant mice. Nature. 1982 Jan 21;295(5846):240–241. doi: 10.1038/295240a0. [DOI] [PubMed] [Google Scholar]
  44. Shaskan E. G., Snyder S. H. Kinetics of serotonin accumulation into slices from rat brain: relationship to catecholamine uptake. J Pharmacol Exp Ther. 1970 Nov;175(2):404–418. [PubMed] [Google Scholar]
  45. Timonen T., Ortaldo J. R., Herberman R. B. Characteristics of human large granular lymphocytes and relationship to natural killer and K cells. J Exp Med. 1981 Mar 1;153(3):569–582. doi: 10.1084/jem.153.3.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Urbina C., Ortiz C., Hurtado I. A new look at basophils in mice. Int Arch Allergy Appl Immunol. 1981;66(2):158–160. doi: 10.1159/000232814. [DOI] [PubMed] [Google Scholar]
  47. Yurt R. W., Leid R. W., Jr, Austen K. F. Native heparin from rat peritoneal mast cells. J Biol Chem. 1977 Jan 25;252(2):518–521. [PubMed] [Google Scholar]
  48. Zagury D., Bernard J., Jeannesson P., Thiernesse N., Cerottini J. C. Studies on the mechanism of T cell-mediated lysis at the single effector cell level. I. Kinetic analysis of lethal hits and target cell lysis in multicellular conjugates. J Immunol. 1979 Oct;123(4):1604–1609. [PubMed] [Google Scholar]

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