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. 1985 Jun 1;161(6):1368–1383. doi: 10.1084/jem.161.6.1368

The Thy-1-bearing cell of murine epidermis. A distinctive leukocyte perhaps related to natural killer cells

PMCID: PMC2187637  PMID: 2861245

Abstract

Bone marrow-derived leukocytes of murine epidermis can express two phenotypes: typical Langerhans cells, which are Ia+ and Thy-1-, and a recently discovered second population that is Thy-1+ and Ia-. To verify that these phenotypes are expressed by two different cell types, and to help understand their lineage and function, we have studied morphology and reactivity with a large panel of antibodies. Dual antibody immunofluorescence combined with electron microscopy showed that Thy-1+ and Ia+ cells were each distributed in a regular fashion and formed adjacent dendritic systems in or close to the basal layer. Double- labeling studies with anti-Ia and a second monoclonal antibody revealed that all Langerhans cells expressed F4/80 (macrophage), Mac-1 (C3bi receptor), and 2.4G2 (Fc receptor), as well as the thymus leukemia (TL) and heat-stable (M1.69/16) antigens. A large fraction expressed S100 and all exhibited membrane ATPase and nonspecific esterase. In contrast, Thy-1+ cells lacked all these features of Langerhans cells, except that a minority were strongly reactive with 2.4G2. Thy-1+ cells also lacked differentiation antigens of most other types of leukocytes, except they were rich in asialo GM1. By electron microscopy, Thy-1+ cells had cytoplasmic granules that were similar in structure and in their aryl sulfatase content to those previously described in natural killer cells. The granules were enlarged in beige mice, suggesting a lysosomal origin, and were present in mast cell-deficient W/Wv mice, indicating no relation to mast cells. We conclude that Thy-1+ epidermal cells are thoroughly distinct from Langerhans cells. On the basis of morphology and phenotype, they may represent a type of tissue natural killer cell. Thy-1+ natural killer cells are now being identified in several nonlymphoid sites, such as gut epithelium and the livers of mice given adjuvants. If Thy-1+ epidermal cells prove to be natural killer cells, it is noteworthy that they represent a resident population regularly distributed in the basal layer of all mouse strains. The notion that Thy-1+ epidermal cells are immature natural killer cells is intriguing in light of recent evidence that Ia+ Langerhans cells are also immature with respect to accessory cell function. The epidermis may not have the functional capacities of a lymphoid organ, but it could contribute immature cells important for both natural and acquired resistance.

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Selected References

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  1. Austyn J. M., Gordon S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol. 1981 Oct;11(10):805–815. doi: 10.1002/eji.1830111013. [DOI] [PubMed] [Google Scholar]
  2. Basch R. S., Berman J. W. Thy-1 determinants are present on many murine hematopoietic cells other than T cells. Eur J Immunol. 1982 May;12(5):359–364. doi: 10.1002/eji.1830120502. [DOI] [PubMed] [Google Scholar]
  3. Bentfeld-Barker M. E., Bainton D. F. Cytochemical localization of arylsulfatase B in rat basophils and mast cells. J Histochem Cytochem. 1980 Oct;28(10):1055–1061. doi: 10.1177/28.10.7419898. [DOI] [PubMed] [Google Scholar]
  4. Bergstresser P. R., Tigelaar R. E., Dees J. H., Streilein J. W. Thy-1 antigen-bearing dendritic cells populate murine epidermis. J Invest Dermatol. 1983 Sep;81(3):286–288. doi: 10.1111/1523-1747.ep12518332. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Breathnach S. M., Katz S. I. Thy-1+ dendritic cells in murine epidermis are bone marrow-derived. J Invest Dermatol. 1984 Jul;83(1):74–77. doi: 10.1111/1523-1747.ep12261808. [DOI] [PubMed] [Google Scholar]
  7. Chan M. M., Tada N., Kimura S., Hoffmann M. K., Miller R. A., Stutman O., Hämmerling U. Characterization of T lymphocyte subsets with monoclonal antibodies: discovery of a distinct marker, Ly-m22, of T suppressor cells. J Immunol. 1983 May;130(5):2075–2078. [PubMed] [Google Scholar]
  8. Coffman R. L., Weissman I. L. A monoclonal antibody that recognizes B cells and B cell precursors in mice. J Exp Med. 1981 Feb 1;153(2):269–279. doi: 10.1084/jem.153.2.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Coffman R. L., Weissman I. L. B220: a B cell-specific member of th T200 glycoprotein family. Nature. 1981 Feb 19;289(5799):681–683. doi: 10.1038/289681a0. [DOI] [PubMed] [Google Scholar]
  10. Dialynas D. P., Wilde D. B., Marrack P., Pierres A., Wall K. A., Havran W., Otten G., Loken M. R., Pierres M., Kappler J. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 1983;74:29–56. doi: 10.1111/j.1600-065x.1983.tb01083.x. [DOI] [PubMed] [Google Scholar]
  11. Dvorak A. M., Galli S. J., Marcum J. A., Nabel G., der Simonian H., Goldin J., Monahan R. A., Pyne K., Cantor H., Rosenberg R. D. Cloned mouse cells with natural killer function and cloned suppressor T cells express ultrastructural and biochemical features not shared by cloned inducer T cells. J Exp Med. 1983 Mar 1;157(3):843–861. doi: 10.1084/jem.157.3.843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gallin J. I., Bujak J. S., Patten E., Wolff S. M. Granulocyte function in the Chediak-Higashi syndrome of mice. Blood. 1974 Feb;43(2):201–206. [PubMed] [Google Scholar]
  13. Goldfischer S. The cytochemical demonstration of lysosomal aryl sulfatase activity by light and electron microscopy. J Histochem Cytochem. 1965 Jul-Aug;13(6):520–523. doi: 10.1177/13.6.520. [DOI] [PubMed] [Google Scholar]
  14. Graham R. C., Jr, Karnovsky M. J. The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem. 1966 Apr;14(4):291–302. doi: 10.1177/14.4.291. [DOI] [PubMed] [Google Scholar]
  15. Granstein R. D., Lowy A., Greene M. I. Epidermal antigen-presenting cells in activation of suppression: identification of a new functional type of ultraviolet radiation-resistant epidermal cell. J Immunol. 1984 Feb;132(2):563–565. [PubMed] [Google Scholar]
  16. Haines K. A., Flotte T. J., Springer T. A., Gigli I., Thorbecke G. J. Staining of Langerhans cells with monoclonal antibodies to macrophages and lymphoid cells. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3448–3451. doi: 10.1073/pnas.80.11.3448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  18. Hume D. A., Robinson A. P., MacPherson G. G., Gordon S. The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80. Relationship between macrophages, Langerhans cells, reticular cells, and dendritic cells in lymphoid and hematopoietic organs. J Exp Med. 1983 Nov 1;158(5):1522–1536. doi: 10.1084/jem.158.5.1522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hurme M., Sihvola M. High expression of the Thy-1 antigen on natural killer cells recently derived from bone marrow. Cell Immunol. 1984 Apr 1;84(2):276–284. doi: 10.1016/0008-8749(84)90099-6. [DOI] [PubMed] [Google Scholar]
  20. Hämmerling G. J., Hämmerling U., Flaherty L. Qat-4 and Qat-5, new murine T-cell antigens governed by the Tla region and identified by monoclonal antibodies. J Exp Med. 1979 Jul 1;150(1):108–116. doi: 10.1084/jem.150.1.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Juhlin L., Shelley W. B. New staining techniques for the Langerhans cell. Acta Derm Venereol. 1977;57(4):289–296. [PubMed] [Google Scholar]
  22. Kasai M., Iwamori M., Nagai Y., Okumura K., Tada T. A glycolipid on the surface of mouse natural killer cells. Eur J Immunol. 1980 Mar;10(3):175–180. doi: 10.1002/eji.1830100304. [DOI] [PubMed] [Google Scholar]
  23. Katz H. R., LeBlanc P. A., Russell S. W. Two classes of mouse mast cells delineated by monoclonal antibodies. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5916–5918. doi: 10.1073/pnas.80.19.5916. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kimura S., Tada N., Liu Y., Hämmerling U. A new mouse cell-surface antigen (Ly-m18) defined by a monoclonal antibody. Immunogenetics. 1981;13(6):547–554. doi: 10.1007/BF00343722. [DOI] [PubMed] [Google Scholar]
  25. Kitamura Y., Go S., Hatanaka K. Decrease of mast cells in W/Wv mice and their increase by bone marrow transplantation. Blood. 1978 Aug;52(2):447–452. [PubMed] [Google Scholar]
  26. Kitano Y., Okada N. Separation of the epidermal sheet by dispase. Br J Dermatol. 1983 May;108(5):555–560. doi: 10.1111/j.1365-2133.1983.tb01056.x. [DOI] [PubMed] [Google Scholar]
  27. Klyczek K. K., Cantor H., Hayes C. E. T cell surface I-J glycoprotein. Concerted action of chromosome-4 and -17 genes forms an epitope dependent on alpha-D-mannosyl residues. J Exp Med. 1984 Jun 1;159(6):1604–1617. doi: 10.1084/jem.159.6.1604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Koo G. C., Peppard J. R. Establishment of monoclonal anti-Nk-1.1 antibody. Hybridoma. 1984 Fall;3(3):301–303. doi: 10.1089/hyb.1984.3.301. [DOI] [PubMed] [Google Scholar]
  29. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. McLean I. W., Nakane P. K. Periodate-lysine-paraformaldehyde fixative. A new fixation for immunoelectron microscopy. J Histochem Cytochem. 1974 Dec;22(12):1077–1083. doi: 10.1177/22.12.1077. [DOI] [PubMed] [Google Scholar]
  32. Mercurio A. M., Schwarting G. A., Robbins P. W. 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. 1984 Oct 1;160(4):1114–1125. doi: 10.1084/jem.160.4.1114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Millard P. J., Henkart M. P., Reynolds C. W., Henkart P. A. Purification and properties of cytoplasmic granules from cytotoxic rat LGL tumors. J Immunol. 1984 Jun;132(6):3197–3204. [PubMed] [Google Scholar]
  34. Minato N., Reid L., Bloom B. R. On the heterogeneity of murine natural killer cells. J Exp Med. 1981 Sep 1;154(3):750–762. doi: 10.1084/jem.154.3.750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Nussenzweig M. C., Steinman R. M., Unkeless J. C., Witmer M. D., Gutchinov B., Cohn Z. A. Studies of the cell surface of mouse dendritic cells and other leukocytes. J Exp Med. 1981 Jul 1;154(1):168–187. doi: 10.1084/jem.154.1.168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Nussenzweig M. C., Steinman R. M., Witmer M. D., Gutchinov B. A monoclonal antibody specific for mouse dendritic cells. Proc Natl Acad Sci U S A. 1982 Jan;79(1):161–165. doi: 10.1073/pnas.79.1.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
  38. Ortaldo J. R., Herberman R. B. Heterogeneity of natural killer cells. Annu Rev Immunol. 1984;2:359–394. doi: 10.1146/annurev.iy.02.040184.002043. [DOI] [PubMed] [Google Scholar]
  39. Ortega G., Robb R. J., Shevach E. M., Malek T. R. The murine IL 2 receptor. I. Monoclonal antibodies that define distinct functional epitopes on activated T cells and react with activated B cells. J Immunol. 1984 Oct;133(4):1970–1975. [PubMed] [Google Scholar]
  40. Podack E. R., Konigsberg P. J. Cytolytic T cell granules. Isolation, structural, biochemical, and functional characterization. J Exp Med. 1984 Sep 1;160(3):695–710. doi: 10.1084/jem.160.3.695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rowden G., Misra B., Higley H., Howard R. Antigens specified by the Tla locus are expressed on the surface of murine Langerhans cells. J Invest Dermatol. 1983 Jul;81(1):2–6. doi: 10.1111/1523-1747.ep12537381. [DOI] [PubMed] [Google Scholar]
  42. Scheid M., Boyse E. A., Carswell E. A., Old L. J. Serologically demonstrable alloantigens of mouse epidermal cells. J Exp Med. 1972 Apr 1;135(4):938–955. doi: 10.1084/jem.135.4.938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Schrader J. W., Battye F., Scollay R. Expression of Thy-1 antigen is not limited to T cells in cultures of mouse hemopoietic cells. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4161–4165. doi: 10.1073/pnas.79.13.4161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Schuler G., Steinman R. M. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med. 1985 Mar 1;161(3):526–546. doi: 10.1084/jem.161.3.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Silver J., Swain S. L., Hubert J. J. Small subunit of I-A subregion antigens determines the allospecificity recognized by a monoclonal antibody. Nature. 1980 Jul 17;286(5770):272–274. doi: 10.1038/286272a0. [DOI] [PubMed] [Google Scholar]
  46. Springer T., Galfré G., Secher D. S., Milstein C. Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur J Immunol. 1979 Apr;9(4):301–306. doi: 10.1002/eji.1830090410. [DOI] [PubMed] [Google Scholar]
  47. Stein K. E., Schwarting G. A., Marcus D. M. Glycolipid markers of murine lymphocyte subpopulations. J Immunol. 1978 Feb;120(2):676–679. [PubMed] [Google Scholar]
  48. Sternberger L. A., Hardy P. H., Jr, Cuculis J. J., Meyer H. G. The unlabeled antibody enzyme method of immunohistochemistry: preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem. 1970 May;18(5):315–333. doi: 10.1177/18.5.315. [DOI] [PubMed] [Google Scholar]
  49. Tagliabue A., Befus A. D., Clark D. A., Bienenstock J. Characteristics of natural killer cells in the murine intestinal epithelium and lamina propria. J Exp Med. 1982 Jun 1;155(6):1785–1796. doi: 10.1084/jem.155.6.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Takei F., Secher D. S., Milstein C., Springer T. Use of a monoclonal antibody specifically non-reactive with T cells to delineate lymphocyte subpopulations. Immunology. 1981 Mar;42(3):371–378. [PMC free article] [PubMed] [Google Scholar]
  51. Takei F., Waldmann H., Lennox E. S., Milstein C. Monoclonal antibody H9/25 reacts with functional subsets of T and B cells: killer, killer precursor and plaque-forming cells. Eur J Immunol. 1980 Jul;10(7):503–509. doi: 10.1002/eji.1830100704. [DOI] [PubMed] [Google Scholar]
  52. Tschachler E., Schuler G., Hutterer J., Leibl H., Wolff K., Stingl G. Expression of Thy-1 antigen by murine epidermal cells. J Invest Dermatol. 1983 Sep;81(3):282–285. doi: 10.1111/1523-1747.ep12518326. [DOI] [PubMed] [Google Scholar]
  53. Unkeless J. C. Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors. J Exp Med. 1979 Sep 19;150(3):580–596. doi: 10.1084/jem.150.3.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Waltenbaugh C. Regulation of immune responses by I-J gene products. I. Production and characterization of anti-I-J monoclonal antibodies. J Exp Med. 1981 Nov 1;154(5):1570–1583. doi: 10.1084/jem.154.5.1570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Wiltrout R. H., Mathieson B. J., Talmadge J. E., Reynolds C. W., Zhang S. R., Herberman R. B., Ortaldo J. R. Augmentation of organ-associated natural killer activity by biological response modifiers. Isolation and characterization of large granular lymphocytes from the liver. J Exp Med. 1984 Nov 1;160(5):1431–1449. doi: 10.1084/jem.160.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Wolff-Schreiner E. C. Ultrastructural cytochemistry of the epidermis. Int J Dermatol. 1977 Mar;16(2):77–102. doi: 10.1111/j.1365-4362.1977.tb01835.x. [DOI] [PubMed] [Google Scholar]
  57. Wolff K., Stingl G. The Langerhans cell. J Invest Dermatol. 1983 Jun;80 (Suppl):17s–21s. [PubMed] [Google Scholar]
  58. Wolff K., Winkelmann R. K. Quantitative studies on the Langerhans cell population of guinea pig epidermis. J Invest Dermatol. 1967 Jun;48(6):504–513. doi: 10.1038/jid.1967.82. [DOI] [PubMed] [Google Scholar]
  59. Young W. W., Jr, Hakomori S. I., Durdik J. M., Henney C. S. Identification of ganglio-N-tetraosylceramide as a new cell surface marker for murine natural killer (NK) cells. J Immunol. 1980 Jan;124(1):199–201. [PubMed] [Google Scholar]
  60. Zucker-Franklin D., Yang J., Fuks A. Different enzyme classes associated with human natural killer cells may mediate disparate functions. J Immunol. 1984 Mar;132(3):1451–1455. [PubMed] [Google Scholar]

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