Abstract
Using granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin 4 we have established dendritic cell (DC) lines from blood mononuclear cells that maintain the antigen capturing and processing capacity characteristic of immature dendritic cells in vivo. These cells have typical dendritic morphology, express high levels of major histocompatibility complex (MHC) class I and class II molecules, CD1, Fc gamma RII, CD40, B7, CD44, and ICAM-1, and lack CD14. Cultured DCs are highly stimulatory in mixed leukocyte reaction (MLR) and are also capable of triggering cord blood naive T cells. Most strikingly, these DCs are as efficient as antigen-specific B cells in presenting tetanus toxoid (TT) to specific T cell clones. Their efficiency of antigen presentation can be further enhanced by specific antibodies via FcR- mediated antigen uptake. Incubation of these cultured DCs with tumor necrosis factor alpha (TNF-alpha) or soluble CD40 ligand (CD40L) for 24 h results in an increased surface expression of MHC class I and class II molecules, B7, and ICAM-1 and in the appearance of the CD44 exon 9 splice variant (CD44-v9); by contrast, Fc gamma RII is markedly and sometimes completely downregulated. The functional consequences of the short contact with TNF-alpha are in increased T cell stimulatory capacity in MLR, but a 10-fold decrease in presentation of soluble TT and a 100-fold decrease in presentation of TT-immunoglobulin G complexes.
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- Aiba S., Katz S. I. The ability of cultured Langerhans cells to process and present protein antigens is MHC-dependent. J Immunol. 1991 Apr 15;146(8):2479–2487. [PubMed] [Google Scholar]
- Austyn J. M. Antigen uptake and presentation by dendritic leukocytes. Semin Immunol. 1992 Aug;4(4):227–236. [PubMed] [Google Scholar]
- Bell E. B., Sparshott S. M. Interconversion of CD45R subsets of CD4 T cells in vivo. Nature. 1990 Nov 8;348(6297):163–166. doi: 10.1038/348163a0. [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]
- Croft M., Duncan D. D., Swain S. L. Response of naive antigen-specific CD4+ T cells in vitro: characteristics and antigen-presenting cell requirements. J Exp Med. 1992 Nov 1;176(5):1431–1437. doi: 10.1084/jem.176.5.1431. [DOI] [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]
- De Bruijn M. L., Nieland J. D., Harding C. V., Melief C. J. Processing and presentation of intact hen egg-white lysozyme by dendritic cells. Eur J Immunol. 1992 Sep;22(9):2347–2352. doi: 10.1002/eji.1830220925. [DOI] [PubMed] [Google Scholar]
- Demotz S., Grey H. M., Sette A. The minimal number of class II MHC-antigen complexes needed for T cell activation. Science. 1990 Aug 31;249(4972):1028–1030. doi: 10.1126/science.2118680. [DOI] [PubMed] [Google Scholar]
- Freudenthal P. S., Steinman R. M. The distinct surface of human blood dendritic cells, as observed after an improved isolation method. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7698–7702. doi: 10.1073/pnas.87.19.7698. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Girolomoni G., Simon J. C., Bergstresser P. R., Cruz P. D., Jr Freshly isolated spleen dendritic cells and epidermal Langerhans cells undergo similar phenotypic and functional changes during short-term culture. J Immunol. 1990 Nov 1;145(9):2820–2826. [PubMed] [Google Scholar]
- Harding C. V., Unanue E. R. Quantitation of antigen-presenting cell MHC class II/peptide complexes necessary for T-cell stimulation. Nature. 1990 Aug 9;346(6284):574–576. doi: 10.1038/346574a0. [DOI] [PubMed] [Google Scholar]
- Harkiss G. D., Hopkins J., McConnell I. Uptake of antigen by afferent lymph dendritic cells mediated by antibody. Eur J Immunol. 1990 Nov;20(11):2367–2373. doi: 10.1002/eji.1830201102. [DOI] [PubMed] [Google Scholar]
- Holt P. G., Oliver J., Bilyk N., McMenamin C., McMenamin P. G., Kraal G., Thepen T. Downregulation of the antigen presenting cell function(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages. J Exp Med. 1993 Feb 1;177(2):397–407. doi: 10.1084/jem.177.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inaba K., Inaba M., Romani N., Aya H., Deguchi M., Ikehara S., Muramatsu S., Steinman R. M. 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):1693–1702. doi: 10.1084/jem.176.6.1693. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inaba K., Romani N., Steinman R. M. An antigen-independent contact mechanism as an early step in T cell-proliferative responses to dendritic cells. J Exp Med. 1989 Aug 1;170(2):527–542. doi: 10.1084/jem.170.2.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inaba K., Schuler G., Witmer M. D., Valinksy J., Atassi B., Steinman R. M. Immunologic properties of purified epidermal Langerhans cells. Distinct requirements for stimulation of unprimed and sensitized T lymphocytes. J Exp Med. 1986 Aug 1;164(2):605–613. doi: 10.1084/jem.164.2.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inaba K., Steinman R. M., Pack M. W., Aya H., Inaba M., Sudo T., Wolpe S., Schuler G. Identification of proliferating dendritic cell precursors in mouse blood. J Exp Med. 1992 May 1;175(5):1157–1167. doi: 10.1084/jem.175.5.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kasinrerk W., Baumruker T., Majdic O., Knapp W., Stockinger H. CD1 molecule expression on human monocytes induced by granulocyte-macrophage colony-stimulating factor. J Immunol. 1993 Jan 15;150(2):579–584. [PubMed] [Google Scholar]
- Koch F., Heufler C., Kämpgen E., Schneeweiss D., Böck G., Schuler G. Tumor necrosis factor alpha maintains the viability of murine epidermal Langerhans cells in culture, but in contrast to granulocyte/macrophage colony-stimulating factor, without inducing their functional maturation. J Exp Med. 1990 Jan 1;171(1):159–171. doi: 10.1084/jem.171.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kämpgen E., Koch N., Koch F., Stöger P., Heufler C., Schuler G., Romani N. Class II major histocompatibility complex molecules of murine dendritic cells: synthesis, sialylation of invariant chain, and antigen processing capacity are down-regulated upon culture. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3014–3018. doi: 10.1073/pnas.88.8.3014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lane P., Brocker T., Hubele S., Padovan E., Lanzavecchia A., McConnell F. Soluble CD40 ligand can replace the normal T cell-derived CD40 ligand signal to B cells in T cell-dependent activation. J Exp Med. 1993 Apr 1;177(4):1209–1213. doi: 10.1084/jem.177.4.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lanzavecchia A. Antigen-specific interaction between T and B cells. Nature. 1985 Apr 11;314(6011):537–539. doi: 10.1038/314537a0. [DOI] [PubMed] [Google Scholar]
- Levine T. P., Chain B. M. Endocytosis by antigen presenting cells: dendritic cells are as endocytically active as other antigen presenting cells. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8342–8346. doi: 10.1073/pnas.89.17.8342. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mamula M. J., Janeway C. A., Jr Do B cells drive the diversification of immune responses? Immunol Today. 1993 Apr;14(4):151–154. doi: 10.1016/0167-5699(93)90274-O. [DOI] [PubMed] [Google Scholar]
- Merkenschlager M., Terry L., Edwards R., Beverley P. C. Limiting dilution analysis of proliferative responses in human lymphocyte populations defined by the monoclonal antibody UCHL1: implications for differential CD45 expression in T cell memory formation. Eur J Immunol. 1988 Nov;18(11):1653–1661. doi: 10.1002/eji.1830181102. [DOI] [PubMed] [Google Scholar]
- Michie C. A., McLean A., Alcock C., Beverley P. C. Lifespan of human lymphocyte subsets defined by CD45 isoforms. Nature. 1992 Nov 19;360(6401):264–265. doi: 10.1038/360264a0. [DOI] [PubMed] [Google Scholar]
- Neefjes J. J., De Bruijn M. L., Boog C. J., Nieland J. D., Boes J., Melief C. J., Ploegh H. L. N-linked glycan modification on antigen-presenting cells restores an allospecific cytotoxic T cell response. J Exp Med. 1990 Feb 1;171(2):583–588. doi: 10.1084/jem.171.2.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Porcelli S., Morita C. T., Brenner M. B. CD1b restricts the response of human CD4-8- T lymphocytes to a microbial antigen. Nature. 1992 Dec 10;360(6404):593–597. doi: 10.1038/360593a0. [DOI] [PubMed] [Google Scholar]
- Puré E., Inaba K., Crowley M. T., Tardelli L., Witmer-Pack M. D., Ruberti G., Fathman G., Steinman R. M. Antigen processing by epidermal Langerhans cells correlates with the level of biosynthesis of major histocompatibility complex class II molecules and expression of invariant chain. J Exp Med. 1990 Nov 1;172(5):1459–1469. doi: 10.1084/jem.172.5.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reid C. D., Stackpoole A., Meager A., Tikerpae J. Interactions of tumor necrosis factor with granulocyte-macrophage colony-stimulating factor and other cytokines in the regulation of dendritic cell growth in vitro from early bipotent CD34+ progenitors in human bone marrow. J Immunol. 1992 Oct 15;149(8):2681–2688. [PubMed] [Google Scholar]
- Romani N., Koide S., Crowley M., Witmer-Pack M., Livingstone A. M., Fathman C. G., Inaba K., Steinman R. M. Presentation of exogenous protein antigens by dendritic cells to T cell clones. Intact protein is presented best by immature, epidermal Langerhans cells. J Exp Med. 1989 Mar 1;169(3):1169–1178. doi: 10.1084/jem.169.3.1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Romani N., Schuler G. The immunologic properties of epidermal Langerhans cells as a part of the dendritic cell system. Springer Semin Immunopathol. 1992;13(3-4):265–279. doi: 10.1007/BF00200527. [DOI] [PubMed] [Google Scholar]
- Rossi G., Heveker N., Thiele B., Gelderblom H., Steinbach F. Development of a Langerhans cell phenotype from peripheral blood monocytes. Immunol Lett. 1992 Feb;31(2):189–197. doi: 10.1016/0165-2478(92)90145-e. [DOI] [PubMed] [Google Scholar]
- 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]
- Sprent J., Schaefer M. Antigen-presenting cells for CD8+ T cells. Immunol Rev. 1990 Oct;117:213–234. doi: 10.1111/j.1600-065x.1990.tb00574.x. [DOI] [PubMed] [Google Scholar]
- Steinman R. M. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271–296. doi: 10.1146/annurev.iy.09.040191.001415. [DOI] [PubMed] [Google Scholar]
- Tazi A., Bouchonnet F., Grandsaigne M., Boumsell L., Hance A. J., Soler P. Evidence that granulocyte macrophage-colony-stimulating factor regulates the distribution and differentiated state of dendritic cells/Langerhans cells in human lung and lung cancers. J Clin Invest. 1993 Feb;91(2):566–576. doi: 10.1172/JCI116236. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas R., Davis L. S., Lipsky P. E. Isolation and characterization of human peripheral blood dendritic cells. J Immunol. 1993 Feb 1;150(3):821–834. [PubMed] [Google Scholar]
- Traunecker A., Oliveri F., Karjalainen K. Myeloma based expression system for production of large mammalian proteins. Trends Biotechnol. 1991 Apr;9(4):109–113. doi: 10.1016/0167-7799(91)90038-j. [DOI] [PubMed] [Google Scholar]
- Zaghouani H., Steinman R., Nonacs R., Shah H., Gerhard W., Bona C. Presentation of a viral T cell epitope expressed in the CDR3 region of a self immunoglobulin molecule. Science. 1993 Jan 8;259(5092):224–227. doi: 10.1126/science.7678469. [DOI] [PubMed] [Google Scholar]