Home LiteratureArticle Details
PMID: 9166413 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

An essential role for CD44 variant isoforms in epidermal Langerhans cell and blood dendritic cell function.

The Journal of cell biology ·Vol. 137 ·No. 5 ·1997-06-02 ·Pages 1137-47

Weiss JM, Sleeman J, Renkl AC, Dittmar H, Termeer CC, Taxis S, Howells N, Hofmann M, Köhler G, Schöpf E, Ponta H, Herrlich P, Simon JC

Abstract

Upon antigen contact, epidermal Langerhans cells (LC) and dendritic cells (DC) leave peripheral organs and home to lymph nodes via the afferent lymphatic vessels and then assemble in the paracortical T cell zone and present antigen to T lymphocytes. Since splice variants of CD44 promote metastasis of certain tumors to lymph nodes, we explored the expression of CD44 proteins on migrating LC and DC. We show that upon antigen contact, LC and DC upregulate pan CD44 epitopes and epitopes encoded by variant exons v4, v5, v6, and v9. Antibodies against CD44 epitopes inhibit the emigration of LC from the epidermis, prevent binding of activated LC and DC to the T cell zones of lymph nodes, and severely inhibit their capacity to induce a delayed type hypersensitivity reaction to a skin hapten in vivo. Our results demonstrate that CD44 splice variant expression is obligatory for the migration and function of LC and DC.

MeSH Terms
Animals Antigen Presentation/physiology Cell Adhesion/immunology Cell Movement/physiology Dendritic Cells/physiology Epitopes/analysis,immunology Female Humans Hyaluronan Receptors/chemistry,physiology Hypersensitivity/immunology Isomerism Langerhans Cells/chemistry,cytology,ultrastructure Lymph Nodes/cytology Mice Mice, Inbred C57BL Microscopy, Electron Rats Rats, Inbred Strains Skin/cytology T-Lymphocytes/cytology,immunology Up-Regulation/immunology
Chemicals
Epitopes Hyaluronan Receptors
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Weiss J M
Department of Dermatology, Freiburg University, D-79104 Freiburg, Germany.
Sleeman J
Renkl A C
Dittmar H
Termeer C C
Taxis S
Howells N
Hofmann M
Köhler G
Schöpf E
Ponta H
Herrlich P
Simon J C
References (52)
52 references, click to expand
  1. Lymphocyte adherence to high endothelial venules: characterization of a modified in vitro assay, and examination of the binding of syngeneic and allogeneic lymphocyte populations.
    J Immunol. 1979 Nov;123(5):1996-2003 PMID: 314954
  2. Mechanism in allergic contact dermatitis.
    Exp Dermatol. 1993 Mar;2(2):63-9 PMID: 8156171
  3. Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85-95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells.
    J Cell Biol. 1987 Aug;105(2):983-90 PMID: 2442176
  4. 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):700-5 PMID: 3279156
  5. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase.
    Gene. 1988 Jul 15;67(1):31-40 PMID: 3047011
  6. Monoclonal antibodies against the CD44 [In(Lu)-related p80], and Pgp-1 antigens in man recognize the Hermes class of lymphocyte homing receptors.
    J Immunol. 1989 Mar 15;142(6):2046-51 PMID: 2646376
  7. CD44 contributes to T cell activation.
    J Immunol. 1989 Aug 1;143(3):798-801 PMID: 2568380
  8. Dual role of the CD44 molecule in T cell adhesion and activation.
    J Immunol. 1989 Oct 15;143(8):2457-63 PMID: 2677141
  9. Antibodies against the CD44 p80, lymphocyte homing receptor molecule augment human peripheral blood T cell activation.
    J Immunol. 1990 Jan 1;144(1):7-15 PMID: 1967267
  10. Monoclonal antibodies to Pgp-1/CD44 block lympho-hemopoiesis in long-term bone marrow cultures.
    J Exp Med. 1990 Feb 1;171(2):477-88 PMID: 2406365
  11. Lymphocyte migration into the skin: the role of lymphocyte homing receptor (CD44) and endothelial cell antigen (HECA-452).
    J Invest Dermatol. 1990 Jun;94(6):786-92 PMID: 1693939
  12. CD44 is the principal cell surface receptor for hyaluronate.
    Cell. 1990 Jun 29;61(7):1303-13 PMID: 1694723
  13. Evidence that cutaneous antigen-presenting cells migrate to regional lymph nodes during contact sensitization.
    J Immunol. 1990 Nov 1;145(9):2833-8 PMID: 2212665
  14. Ultraviolet B radiation converts Langerhans cells from immunogenic to tolerogenic antigen-presenting cells. Induction of specific clonal anergy in CD4+ T helper 1 cells.
    J Immunol. 1991 Jan 15;146(2):485-91 PMID: 1670944
  15. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells.
    Cell. 1991 Apr 5;65(1):13-24 PMID: 1707342
  16. Early molecular events in the induction phase of contact sensitivity.
    Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1398-402 PMID: 1741395
  17. Participation in normal immune responses of a metastasis-inducing splice variant of CD44.
    Science. 1992 Jul 31;257(5070):682-5 PMID: 1496383
  18. CD44H regulates tumor cell migration on hyaluronate-coated substrate.
    J Cell Biol. 1992 Aug;118(4):971-7 PMID: 1380003
  19. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor.
    J Exp Med. 1992 Dec 1;176(6):1693-702 PMID: 1460426
  20. Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons.
    Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12160-4 PMID: 1465456
  21. T-cell adhesion induced by proteoglycan-immobilized cytokine MIP-1 beta.
    Nature. 1993 Jan 7;361(6407):79-82 PMID: 7678446
  22. Prevention of tumor metastasis formation by anti-variant CD44.
    J Exp Med. 1993 Feb 1;177(2):443-55 PMID: 8426113
  23. Migration of human melanoma cells on hyaluronate is related to CD44 expression.
    J Invest Dermatol. 1993 Feb;100(2):115-20 PMID: 8429233
  24. A link between ras and metastatic behavior of tumor cells: ras induces CD44 promoter activity and leads to low-level expression of metastasis-specific variants of CD44 in CREF cells.
    Cancer Res. 1993 Apr 1;53(7):1516-21 PMID: 8453616
  25. Activated human lymphocytes and aggressive non-Hodgkin's lymphomas express a homologue of the rat metastasis-associated variant of CD44.
    J Exp Med. 1993 Apr 1;177(4):897-904 PMID: 8459220
  26. Splicing choice from ten variant exons establishes CD44 variability.
    Nucleic Acids Res. 1993 Mar 11;21(5):1225-9 PMID: 8464707
  27. CD44 is necessary for optimal contact allergic responses but is not required for normal leukocyte extravasation.
    J Exp Med. 1993 Aug 1;178(2):497-507 PMID: 8340756
  28. Dendritic cells: antigen presentation, accessory function and clinical relevance.
    Adv Exp Med Biol. 1993;329:1-9 PMID: 8379358
  29. Modulation of epidermal Langerhans' cell frequency by tumour necrosis factor-alpha.
    Immunology. 1994 Mar;81(3):395-401 PMID: 7911448
  30. Expression of the B7/BB1 activation antigen and its ligand CD28 in T-cell-mediated skin diseases.
    J Invest Dermatol. 1994 Oct;103(4):539-43 PMID: 7523532
  31. Both dendritic cells and memory T lymphocytes emigrate from organ cultures of human skin and form distinctive dendritic-T-cell conjugates.
    J Invest Dermatol. 1995 Jan;104(1):11-7 PMID: 7798627
  32. CD44 isoforms containing exon V3 are responsible for the presentation of heparin-binding growth factor.
    J Cell Biol. 1995 Feb;128(4):687-98 PMID: 7532176
  33. In vivo evidence that ultraviolet B-induced suppression of allergic contact sensitivity is associated with functional inactivation of Th1 cells.
    Photodermatol Photoimmunol Photomed. 1994 Oct;10(5):206-11 PMID: 7880760
  34. Lymph node (but not spleen) invasion by murine lymphoma is both CD44- and hyaluronate-dependent.
    J Immunol. 1995 May 15;154(10):5345-55 PMID: 7537306
  35. H blood group antigen carried by CD44V modulates tumorigenicity of rat colon carcinoma cells.
    Cancer Res. 1994 Dec 1;54(23):6275-81 PMID: 7525057
  36. CD44 variant isoforms in non-Hodgkin's lymphoma: a new independent prognostic factor.
    Blood. 1995 May 15;85(10):2885-99 PMID: 7537983
  37. Contact sensitivity as a model for T-cell activation in skin.
    J Invest Dermatol. 1995 Jul;105(1 Suppl):80S-83S PMID: 7616003
  38. CD44 is the major peanut lectin-binding glycoprotein of human epidermal keratinocytes and plays a role in intercellular adhesion.
    J Cell Sci. 1995 May;108 ( Pt 5):1959-70 PMID: 7544799
  39. Rapid purification of human Langerhans cells using paramagnetic microbeads.
    Exp Dermatol. 1995 Jun;4(3):155-61 PMID: 7551563
  40. Removal of the majority of epidermal Langerhans cells by topical or systemic steroid application enhances the effector phase of murine contact hypersensitivity.
    J Immunol. 1995 Nov 1;155(9):4207-17 PMID: 7594576
  41. Low-dose UVB radiation perturbs the functional expression of B7.1 and B7.2 co-stimulatory molecules on human Langerhans cells.
    Eur J Immunol. 1995 Oct;25(10):2858-62 PMID: 7589083
  42. Regulation of CD44 binding to hyaluronan by glycosylation of variably spliced exons.
    J Cell Biol. 1995 Dec;131(6 Pt 1):1623-33 PMID: 8522617
  43. Receptor-ligand interaction between CD44 and osteopontin (Eta-1).
    Science. 1996 Jan 26;271(5248):509-12 PMID: 8560266
  44. Cell migration: a physically integrated molecular process.
    Cell. 1996 Feb 9;84(3):359-69 PMID: 8608589
  45. New insights into the mobilization and phagocytic activity of dendritic cells.
    J Exp Med. 1996 Apr 1;183(4):1287-92 PMID: 8666885
  46. Accelerated immune response in transgenic mice expressing rat CD44v4-v7 on T cells.
    J Immunol. 1996 Mar 15;156(6):2085-94 PMID: 8690896
  47. Murine epidermal Langerhans cells as a model to study tissue dendritic cells.
    Adv Exp Med Biol. 1993;329:243-9 PMID: 8379377
  48. CD44 splice variants: metastases meet lymphocytes.
    Immunol Today. 1993 Aug;14(8):395-9 PMID: 7691067
  49. F(ab) secondary antibodies: a general method for double immunolabeling with primary antisera from the same species. Efficiency control by chemiluminescence.
    J Histochem Cytochem. 1994 Mar;42(3):433-7 PMID: 7508473
  50. 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):1109-18 PMID: 8145033
  51. CD44 isoform expression mediated by alternative splicing: tissue-specific regulation in mice.
    Int Immunol. 1994 Jan;6(1):49-59 PMID: 7511928
  52. A monoclonal antibody specifically reactive to human Langerhans cells.
    J Invest Dermatol. 1986 Nov;87(5):602-7 PMID: 3534103
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.137.5.1137
Published
1997-06-02
Pages
1137-47
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2136215
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.137.5.1137 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2