Abstract
Different reasons account for the lack of information about the expression of cytokine receptors on human dendritic cells (DC): (a) DC are a trace population; (b) the proteolytic treatment used to isolate DC may alter enzyme-sensitive epitopes; and (c) low numbers of receptors per cell. In the present work the expression of cytokine receptors was analysed by flow cytometry on the population of dermal DC (DDC) that spontaneously migrate from short-term culture dermal explants. DDC obtained after dermal culture were CD1alow, CD1b+, CD1c+, human leucocyte antigen (HLA)-DR+, CD11chigh, CD11b+ and CD32+. The DC lineage was confirmed by ultrastructural analysis. DDC expressed interleukin (IL)-1R type 1 (monoclonal antibody (mAb) hIL-1R1-M1; and 6B5); IL-1R type 2 (mAb hIL-1R2-M22); IL-2R alpha chain (mAb anti-Tac; and hIL-2R-M1) and IL-2R gamma chain (mAb 3B5; and AG14C). DDC did not stain for IL-2R beta chain using four mAbs recognizing two different epitopes of IL-2R beta (mAb 2R-B; Mik-beta 1; and CF1; Mik-beta 3, respectively). DDC were also positive for the cytokine binding chains (alpha chains) of IL-3R (mAb 9F5); IL-4R (mAb hIL-4R-M57; and S456C9); and IL-7R (mAb hIL-7R-M20; and R3434). DDC showed low levels of IL-6R alpha chain (mAb B-F19; B-R6; and B-E23) and its signal transducer gp130 (mAb A2; and B1). DDC strongly expressed interferon-gamma receptor (IFN-gamma R) (mAb GIR-208) and were negative for IL-8R (mAb B-G20; and B-F25). All DDC were highly positive for granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) alpha chain (mAb hGM-CSFR-M1; SC06; SC04, and 8G6) and to a lesser extent for the common beta chain of GM-CSFR, IL-3R and IL-5R (mAb 3D7). On the other hand, reactivity was not found for granulocyte colony-stimulating factor receptor (G-CSFR) (mAb hGCSFR-M1) nor macrophage colony-stimulating factor receptor (M-CSFR) (mAb 7-7A3-17) confirming the DC lineage of DDC. As previously reported for lymphoid DC, DDC expressed tumour necrosis factor receptort (TNFR) 75000 MW (mAb utr-1; hTNFR-M1; and MR2-1) but lacked TNFR 55000 MW (mAb htr-9; MR1-1; and MR1-2). In summary, DDC express receptors for a broad panel of cytokines, even receptors for cytokines whose effects on DC are still unknown (i.e. IL-2R alpha gamma; IL-6R alpha/gp 130; IL-7R alpha gamma).
Full text
PDF










Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bieber T., Rieger A., Neuchrist C., Prinz J. C., Rieber E. P., Boltz-Nitulescu G., Scheiner O., Kraft D., Ring J., Stingl G. Induction of Fc epsilon R2/CD23 on human epidermal Langerhans cells by human recombinant interleukin 4 and gamma interferon. J Exp Med. 1989 Jul 1;170(1):309–314. doi: 10.1084/jem.170.1.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Braverman I. M., Sibley J., Keh-Yen A. A study of the veil cells around normal, diabetic, and aged cutaneous microvessels. J Invest Dermatol. 1986 Jan;86(1):57–62. doi: 10.1111/1523-1747.ep12283816. [DOI] [PubMed] [Google Scholar]
- Buckley C. C., Ivison C., Poulter L. W., Rustin M. H. Fc epsilon R11/CD23 receptor distribution in patch test reactions to aeroallergens in atopic dermatitis. J Invest Dermatol. 1992 Aug;99(2):184–188. doi: 10.1111/1523-1747.ep12616813. [DOI] [PubMed] [Google Scholar]
- Caux C., Dezutter-Dambuyant C., Schmitt D., Banchereau J. GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature. 1992 Nov 19;360(6401):258–261. doi: 10.1038/360258a0. [DOI] [PubMed] [Google Scholar]
- Caux C., Vanbervliet B., Massacrier C., Durand I., Banchereau J. Interleukin-3 cooperates with tumor necrosis factor alpha for the development of human dendritic/Langerhans cells from cord blood CD34+ hematopoietic progenitor cells. Blood. 1996 Mar 15;87(6):2376–2385. [PubMed] [Google Scholar]
- Cerio R., Griffiths C. E., Cooper K. D., Nickoloff B. J., Headington J. T. Characterization of factor XIIIa positive dermal dendritic cells in normal and inflamed skin. Br J Dermatol. 1989 Oct;121(4):421–431. doi: 10.1111/j.1365-2133.1989.tb15509.x. [DOI] [PubMed] [Google Scholar]
- Cerio R., Spaull J., Oliver G. F., Jones W. E. A study of factor XIIIa and MAC 387 immunolabeling in normal and pathological skin. Am J Dermatopathol. 1990 Jun;12(3):221–233. doi: 10.1097/00000372-199006000-00002. [DOI] [PubMed] [Google Scholar]
- Chang C. H., Furue M., Tamaki K. B7-1 expression of Langerhans cells is up-regulated by proinflammatory cytokines, and is down-regulated by interferon-gamma or by interleukin-10. Eur J Immunol. 1995 Feb;25(2):394–398. doi: 10.1002/eji.1830250213. [DOI] [PubMed] [Google Scholar]
- Chang C. H., Furue M., Tamaki K. Selective regulation of ICAM-1 and major histocompatibility complex class I and II molecule expression on epidermal Langerhans cells by some of the cytokines released by keratinocytes and T cells. Eur J Immunol. 1994 Nov;24(11):2889–2895. doi: 10.1002/eji.1830241146. [DOI] [PubMed] [Google Scholar]
- Cumberbatch M., Fielding I., Kimber I. Modulation of epidermal Langerhans' cell frequency by tumour necrosis factor-alpha. Immunology. 1994 Mar;81(3):395–401. [PMC free article] [PubMed] [Google Scholar]
- Cumberbatch M., Kimber I. Dermal tumour necrosis factor-alpha induces dendritic cell migration to draining lymph nodes, and possibly provides one stimulus for Langerhans' cell migration. Immunology. 1992 Feb;75(2):257–263. [PMC free article] [PubMed] [Google Scholar]
- Cumberbatch M., Kimber I. Phenotypic characteristics of antigen-bearing cells in the draining lymph nodes of contact sensitized mice. Immunology. 1990 Nov;71(3):404–410. [PMC free article] [PubMed] [Google Scholar]
- Elbaz O., Budel L. M., Hoogerbrugge H., Touw I. P., Delwel R., Mahmoud L. A., Löwenberg B. Tumor necrosis factor regulates the expression of granulocyte-macrophage colony-stimulating factor and interleukin-3 receptors on human acute myeloid leukemia cells. Blood. 1991 Mar 1;77(5):989–995. [PubMed] [Google Scholar]
- Enk A. H., Angeloni V. L., Udey M. C., Katz S. I. An essential role for Langerhans cell-derived IL-1 beta in the initiation of primary immune responses in skin. J Immunol. 1993 May 1;150(9):3698–3704. [PubMed] [Google Scholar]
- Heufler C., Koch F., Schuler G. Granulocyte/macrophage colony-stimulating factor and interleukin 1 mediate the maturation of murine epidermal Langerhans cells into potent immunostimulatory dendritic cells. J Exp Med. 1988 Feb 1;167(2):700–705. doi: 10.1084/jem.167.2.700. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heufler C., Topar G., Grasseger A., Stanzl U., Koch F., Romani N., Namen A. E., Schuler G. Interleukin 7 is produced by murine and human keratinocytes. J Exp Med. 1993 Sep 1;178(3):1109–1114. doi: 10.1084/jem.178.3.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Knight S. C., Stagg A. J. Antigen-presenting cell types. Curr Opin Immunol. 1993 Jun;5(3):374–382. doi: 10.1016/0952-7915(93)90056-x. [DOI] [PubMed] [Google Scholar]
- Koide S. L., Inaba K., Steinman R. M. Interleukin 1 enhances T-dependent immune responses by amplifying the function of dendritic cells. J Exp Med. 1987 Feb 1;165(2):515–530. doi: 10.1084/jem.165.2.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kämpgen E., Koch F., Heufler C., Eggert A., Gill L. L., Gillis S., Dower S. K., Romani N., Schuler G. Understanding the dendritic cell lineage through a study of cytokine receptors. J Exp Med. 1994 Jun 1;179(6):1767–1776. doi: 10.1084/jem.179.6.1767. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Larregina A., Morelli A., Kolkowski E., Fainboim L. Flow cytometric analysis of cytokine receptors on human Langerhans' cells. Changes observed after short-term culture. Immunology. 1996 Feb;87(2):317–325. doi: 10.1046/j.1365-2567.1996.451513.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Larsen C. P., Ritchie S. C., Hendrix R., Linsley P. S., Hathcock K. S., Hodes R. J., Lowry R. P., Pearson T. C. Regulation of immunostimulatory function and costimulatory molecule (B7-1 and B7-2) expression on murine dendritic cells. J Immunol. 1994 Jun 1;152(11):5208–5219. [PubMed] [Google Scholar]
- Larsen C. P., Steinman R. M., Witmer-Pack M., Hankins D. F., Morris P. J., Austyn J. M. Migration and maturation of Langerhans cells in skin transplants and explants. J Exp Med. 1990 Nov 1;172(5):1483–1493. doi: 10.1084/jem.172.5.1483. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lenz A., Heine M., Schuler G., Romani N. Human and murine dermis contain dendritic cells. Isolation by means of a novel method and phenotypical and functional characterization. J Clin Invest. 1993 Dec;92(6):2587–2596. doi: 10.1172/JCI116873. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lundqvist E. N., Bäck O. Interleukin-1 decreases the number of Ia+ epidermal dendritic cells but increases their expression of Ia antigen. Acta Derm Venereol. 1990;70(5):391–394. [PubMed] [Google Scholar]
- Macatonia S. E., Knight S. C., Edwards A. J., Griffiths S., Fryer P. Localization of antigen on lymph node dendritic cells after exposure to the contact sensitizer fluorescein isothiocyanate. Functional and morphological studies. J Exp Med. 1987 Dec 1;166(6):1654–1667. doi: 10.1084/jem.166.6.1654. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miyajima A., Kitamura T., Harada N., Yokota T., Arai K. Cytokine receptors and signal transduction. Annu Rev Immunol. 1992;10:295–331. doi: 10.1146/annurev.iy.10.040192.001455. [DOI] [PubMed] [Google Scholar]
- Mohamadzadeh M., Ariizumi K., Sugamura K., Bergstresser P. R., Takashima A. Expression of the common cytokine receptor gamma chain by murine dendritic cells including epidermal Langerhans cells. Eur J Immunol. 1996 Jan;26(1):156–160. doi: 10.1002/eji.1830260124. [DOI] [PubMed] [Google Scholar]
- Murphy G. F., Bhan A. K., Harrist T. J., Mihm M. C., Jr In situ identification of T6-positive cells in normal human dermis by immunoelectron microscopy. Br J Dermatol. 1983 Apr;108(4):423–431. doi: 10.1111/j.1365-2133.1983.tb04594.x. [DOI] [PubMed] [Google Scholar]
- Nestle F. O., Zheng X. G., Thompson C. B., Turka L. A., Nickoloff B. J. Characterization of dermal dendritic cells obtained from normal human skin reveals phenotypic and functionally distinctive subsets. J Immunol. 1993 Dec 1;151(11):6535–6545. [PubMed] [Google Scholar]
- Roake J. A., Rao A. S., Morris P. J., Larsen C. P., Hankins D. F., Austyn J. M. Dendritic cell loss from nonlymphoid tissues after systemic administration of lipopolysaccharide, tumor necrosis factor, and interleukin 1. J Exp Med. 1995 Jun 1;181(6):2237–2247. doi: 10.1084/jem.181.6.2237. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Romani N., Gruner S., Brang D., Kämpgen E., Lenz A., Trockenbacher B., Konwalinka G., Fritsch P. O., Steinman R. M., Schuler G. Proliferating dendritic cell progenitors in human blood. J Exp Med. 1994 Jul 1;180(1):83–93. doi: 10.1084/jem.180.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Romani N., Gruner S., Brang D., Kämpgen E., Lenz A., Trockenbacher B., Konwalinka G., Fritsch P. O., Steinman R. M., Schuler G. Proliferating dendritic cell progenitors in human blood. J Exp Med. 1994 Jul 1;180(1):83–93. doi: 10.1084/jem.180.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Romani N., Lenz A., Glassel H., Stössel H., Stanzl U., Majdic O., Fritsch P., Schuler G. Cultured human Langerhans cells resemble lymphoid dendritic cells in phenotype and function. J Invest Dermatol. 1989 Nov;93(5):600–609. doi: 10.1111/1523-1747.ep12319727. [DOI] [PubMed] [Google Scholar]
- Sallusto F., Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med. 1994 Apr 1;179(4):1109–1118. doi: 10.1084/jem.179.4.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Santiago-Schwarz F., Divaris N., Kay C., Carsons S. E. Mechanisms of tumor necrosis factor-granulocyte-macrophage colony-stimulating factor-induced dendritic cell development. Blood. 1993 Nov 15;82(10):3019–3028. [PubMed] [Google Scholar]
- Scaletta L. J., MacCallum D. K. A fine structural study of divalent cation-mediated epithelial union with connective tissue in human oral mucosa. Am J Anat. 1972 Apr;133(4):431–453. doi: 10.1002/aja.1001330406. [DOI] [PubMed] [Google Scholar]
- Sepulveda-Merrill C., Mayall S., Hamblin A. S., Breathnach S. M. Antigen-presenting capacity in normal human dermis is mainly subserved by CD1a+ cells. Br J Dermatol. 1994 Jul;131(1):15–22. doi: 10.1111/j.1365-2133.1994.tb08451.x. [DOI] [PubMed] [Google Scholar]
- Sontheimer R. D., Matsubara T., Seelig L. L., Jr A macrophage phenotype for a constitutive, class II antigen-expressing, human dermal perivascular dendritic cell. J Invest Dermatol. 1989 Jul;93(1):154–159. doi: 10.1111/1523-1747.ep12277390. [DOI] [PubMed] [Google Scholar]
- Sreilein J. W. Antigen-presenting cells in the induction of contact hypersensitivity in mice: evidence that Langerhans cells are sufficient but not required. J Invest Dermatol. 1989 Oct;93(4):443–448. doi: 10.1111/1523-1747.ep12284018. [DOI] [PubMed] [Google Scholar]
- Steiner G., Tschachler E., Tani M., Malek T. R., Shevach E. M., Holter W., Knapp W., Wolff K., Stingl G. Interleukin 2 receptors on cultured murine epidermal Langerhans cells. J Immunol. 1986 Jul 1;137(1):155–159. [PubMed] [Google Scholar]
- Sueki H., Whitaker D., Buchsbaum M., Murphy G. F. Novel interactions between dermal dendrocytes and mast cells in human skin. Implications for hemostasis and matrix repair. Lab Invest. 1993 Aug;69(2):160–172. [PubMed] [Google Scholar]
- Sugamura K., Asao H., Kondo M., Tanaka N., Ishii N., Ohbo K., Nakamura M., Takeshita T. The interleukin-2 receptor gamma chain: its role in the multiple cytokine receptor complexes and T cell development in XSCID. Annu Rev Immunol. 1996;14:179–205. doi: 10.1146/annurev.immunol.14.1.179. [DOI] [PubMed] [Google Scholar]
- Tse Y., Cooper K. D. Cutaneous dermal Ia+ cells are capable of initiating delayed type hypersensitivity responses. J Invest Dermatol. 1990 Mar;94(3):267–272. doi: 10.1111/1523-1747.ep12874114. [DOI] [PubMed] [Google Scholar]
- Watanabe Y., Kitamura T., Hayashida K., Miyajima A. Monoclonal antibody against the common beta subunit (beta c) of the human interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor receptors shows upregulation of beta c by IL-1 and tumor necrosis factor-alpha. Blood. 1992 Nov 1;80(9):2215–2220. [PubMed] [Google Scholar]
- Witmer-Pack M. D., Olivier W., Valinsky J., Schuler G., Steinman R. M. Granulocyte/macrophage colony-stimulating factor is essential for the viability and function of cultured murine epidermal Langerhans cells. J Exp Med. 1987 Nov 1;166(5):1484–1498. doi: 10.1084/jem.166.5.1484. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van de Rijn M., Lerch P. G., Bronstein B. R., Knowles R. W., Bhan A. K., Terhorst C. Human cutaneous dendritic cells express two glycoproteins T6 and M241 which are biochemically identical to those found on cortical thymocytes. Hum Immunol. 1984 Apr;9(4):201–210. doi: 10.1016/0198-8859(84)90025-9. [DOI] [PubMed] [Google Scholar]

