{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:26:38Z","timestamp":1791120398724,"version":"4.1.0"},"reference-count":41,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5415","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1999,4,30]]},"abstract":"<jats:p>Langerhans' cells migrating from contact-sensitized skin were found to up-regulate expression of macrophage-derived chemokine (MDC) during maturation into lymph node dendritic cells (DCs). Na\u0131\u0308ve T cells did not migrate toward MDC, but antigen-specific T cells rapidly acquired MDC responsiveness in vivo after a subcutaneous injection of antigen. In chemotaxis assays, maturing DCs attracted activated T cells more strongly than na\u0131\u0308ve T cells. These studies identified chemokine up-regulation as part of the Langerhans' cell maturation program to immunogenic T cell\u2013zone DC. Preferential recruitment of activated T cells may be a mechanism used by maturing DCs to promote encounters with antigen-specific T cells.<\/jats:p>","DOI":"10.1126\/science.284.5415.819","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:37:20Z","timestamp":1027762640000},"page":"819-822","source":"Crossref","is-referenced-by-count":247,"title":["Chemokine Up-Regulation and Activated T Cell Attraction by Maturing Dendritic Cells"],"prefix":"10.1126","volume":"284","author":[{"given":"H. Lucy","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason G.","family":"Cyster","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/32588"},{"key":"e_1_3_1_2_3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1600-065X.1997.tb00956.x","volume":"156","author":"Steinman R. M.","year":"1997","unstructured":"Steinman R. M., Pack M., Inaba K., Immunol. Rev. 156, 25 (1997);","journal-title":"Immunol. Rev."},{"key":"e_1_3_1_2_4","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/stem.150409","volume":"15","author":"Shortman K.","year":"1997","unstructured":"Shortman K., Caux C. J., Stem Cells 15, 409 (1997).","journal-title":"Stem Cells"},{"key":"e_1_3_1_3_2","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/42716","volume":"387","author":"Adema G. J.","year":"1997","unstructured":"Adema G. J., et al., Nature 387, 713 (1997).","journal-title":"Nature"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.6.875"},{"key":"e_1_3_1_5_2","first-page":"181","volume":"188","author":"Ngo V. N.","year":"1998","unstructured":"Ngo V. N., Tang H. L., Cyster J. G., ibid. 188, 181 (1998).","journal-title":"ibid."},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","unstructured":"R. Godiska et al. ibid. 185 1595 (1997);","DOI":"10.1084\/jem.185.9.1595"},{"key":"e_1_3_1_6_3","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/jlb.63.5.606","volume":"63","author":"Rodenburg R. J.","year":"1998","unstructured":"Rodenburg R. J., et al., J. Leukocyte Biol. 63, 606 (1998).","journal-title":"J. Leukocyte Biol."},{"key":"e_1_3_1_7_2","doi-asserted-by":"crossref","first-page":"25229","DOI":"10.1074\/jbc.272.40.25229","volume":"272","author":"Chang M.","year":"1997","unstructured":"Chang M., et al., J. Biol. Chem. 272, 25229 (1997).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_1_8_2","doi-asserted-by":"crossref","first-page":"5027","DOI":"10.4049\/jimmunol.161.9.5027","volume":"161","author":"Andrew D. P.","year":"1998","unstructured":"Andrew D. P., et al., J. Immunol. 161, 5027 (1998).","journal-title":"J. Immunol."},{"key":"e_1_3_1_9_2","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1084\/jem.188.3.451","volume":"188","author":"Schaniel C.","year":"1998","unstructured":"Schaniel C., et al., J. Exp. Med. 188, 451 (1998).","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_10_2","unstructured":"BLAST searches of the National Center for Biotechnology Information expressed sequence tag (EST) database for mouse chemokine sequences identified one mouse EST () that encoded a 92\u2013amino acid protein with 64% identity to human MDC. This sequence is identical to the recently described mouse ABCD1 sequence (8). An 800\u2013base pair Eco RI fragment containing the coding region was used as a probe for Northern blot analysis and digoxigenin-based in situ hybridization was performed as described (4). RT-PCR was performed with primers specific for MDC (5\u2032-GTGGCTCTCGTCCTTCTTGC-3\u2032 and 5\u2032-GGACAGTTTATGGAGTAGCTT-3\u2032) ELC (4) or actin. Mature mouse MDC (amino acids 25 to 92) was expressed in Escherichia coli as described for ELC (4)."},{"key":"e_1_3_1_11_2","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1074\/jbc.273.3.1764","volume":"273","author":"Imai T.","year":"1998","unstructured":"Imai T., et al., J. Biol. Chem. 273, 1764 (1998).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_1_12_2","doi-asserted-by":"crossref","first-page":"4448","DOI":"10.1182\/blood.V89.12.4448","volume":"89","author":"Youn B. S.","year":"1997","unstructured":"Youn B. S., et al., Blood 89, 4448 (1997).","journal-title":"Blood"},{"key":"e_1_3_1_13_2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1006\/bbrc.1996.0059","volume":"218","author":"Hoogewerf A.","year":"1996","unstructured":"Hoogewerf A., Black D., Proudfoot A. E., Wells T. N., Power C. A., Biochem. Biophys. Res. Commun. 218, 337 (1996).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"e_1_3_1_14_2","unstructured":"Full-length mouse CCR4 (11 12) isolated by RT-PCR was subcloned into a modified form of pEF-BOS ["},{"key":"e_1_3_1_14_3","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/18.17.5322"},{"key":"e_1_3_1_14_4","unstructured":"] and transfected into E300-19 pre-B cells (4). The published mouse CCR4 sequences have nine amino acid differences (11 12). Our sequence matched one or other of the published sequences at each of the nine positions: Ser 145 Glu 181 Val 241 and Phe 311 as in (11) and Ile 4 Asp 205 Cys 221 Ala 246 and Ala 293 as in (12)."},{"key":"e_1_3_1_15_2","unstructured":"H. L. Tang and J. G. Cyster unpublished observations."},{"key":"e_1_3_1_16_2","doi-asserted-by":"crossref","first-page":"21514","DOI":"10.1074\/jbc.271.35.21514","volume":"271","author":"Imai T.","year":"1996","unstructured":"Imai T., et al., J. Biol. Chem. 271, 21514 (1996);","journal-title":"J. Biol. Chem."},{"key":"e_1_3_1_16_3","first-page":"15036","volume":"272","author":"Imai T.","year":"1997","unstructured":"Imai T., et al., ibid. 272, 15036 (1997).","journal-title":"ibid."},{"key":"e_1_3_1_17_2","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/0923-2494(89)90048-5","volume":"140","author":"Fossum S.","year":"1989","unstructured":"Fossum S., Res. Immunol. 140, 883 (1989).","journal-title":"Res. Immunol."},{"key":"e_1_3_1_18_2","first-page":"21","volume":"39","author":"Thomas W. R.","year":"1980","unstructured":"Thomas W. R., Edwards A. J., Watkins M. C., Asherson G. L., Immunology 39, 21 (1980);","journal-title":"Immunology"},{"key":"e_1_3_1_18_3","first-page":"509","volume":"59","author":"Macatonia S. E.","year":"1986","unstructured":"Macatonia S. E., Edwards A. J., Knight S. C., ibid. 59, 509 (1986);","journal-title":"ibid."},{"key":"e_1_3_1_18_4","unstructured":"; S. Hill A. J. Edwards I. Kimber S. C. Knight ibid. 71 277 (1990);"},{"key":"e_1_3_1_18_5","doi-asserted-by":"crossref","first-page":"6148","DOI":"10.4049\/jimmunol.159.12.6148","volume":"159","author":"Wang B.","year":"1997","unstructured":"Wang B., et al., J. Immunol. 159, 6148 (1997).","journal-title":"J. Immunol."},{"key":"e_1_3_1_19_2","unstructured":"Skin was sensitized as described (17). Mice shown in Fig. 2A were painted on the shaved thorax and abdomen with 0.4 ml of 2% FITC (Sigma) dissolved in a 1:1 (v\/v) acetone\/dibutyl phthalate (Sigma) mixture and RNA was prepared from pooled brachial inguinal and axillary nodes. For other experiments a region of mouse skin on the arm or flank was shaved 25 \u03bcl of 1% FITC in acetone\/dibutyl phthalate was applied onto each region and the draining nodes (brachial and inguinal) were analyzed 1 day later."},{"key":"e_1_3_1_20_2","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1084\/jem.184.4.1413","volume":"184","author":"De Smedt T.","year":"1996","unstructured":"De Smedt T., et al., J. Exp. Med. 184, 1413 (1996).","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_21_2","first-page":"1654","volume":"166","author":"Macatonia S. E.","year":"1987","unstructured":"Macatonia S. E., Knight S. C., Edwards A. J., Griffiths S., Fryer P., ibid. 166, 1654 (1987).","journal-title":"ibid."},{"key":"e_1_3_1_22_2","unstructured":"Mouse ear epidermal cells were isolated and cultured as described (22). In some cases cells were stained with anti\u2013MHC class II (I-A b ) sorted to >93% MHC class II high LCs and used for RNA preparation. To purify DCs that were newly migrating into lymph nodes we painted the skin of mice with FITC (18) and 1 day later we collected draining lymph nodes and gently mashed them through a 70-\u03bcm mesh cell strainer. DCs in cell suspensions prepared without enzymatic digestion were enriched for FITC + cells which is consistent with findings that monocyte-derived DCs are more easily isolated from lymphoid tissues than other DC types (1). To prepare RNA we sorted DCs to >95% B220 \u2013 FITC + I-A b -hi cells. For chemotaxis assays DCs from \u223c18 FITC-painted mice per experiment were enriched with metrizamide and either immediately put into culture or first sorted to >90% B220 \u2013 CD11c + . Cells were cultured in serum-free medium (Mediatech Herndon VA) at 2 \u00d7 10 6 to 5 \u00d7 10 6 cells\/ml for 1 day. The stromal material that did not enter suspension after mechanical mashing contained SLC-expressing cells and ELC-expressing resident DCs (4 14). Stromal preparations from 30 to 40 brachial and axillary nodes per experiment were cultured overnight in 2 ml of serum-free medium to provide supernatant for chemotaxis assays."},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.161.3.526"},{"key":"e_1_3_1_23_3","first-page":"1169","volume":"169","author":"Romani N.","year":"1989","unstructured":"Romani N., et al., ibid. 169, 1169 (1989);","journal-title":"ibid."},{"key":"e_1_3_1_23_4","doi-asserted-by":"crossref","unstructured":"; C. Heufler et al. ibid. 176 1221 (1992).","DOI":"10.1084\/jem.176.4.1221"},{"key":"e_1_3_1_24_2","doi-asserted-by":"crossref","unstructured":"R. Bonecchi et al. ibid. 187 129 (1998).","DOI":"10.1084\/jem.187.1.129"},{"key":"e_1_3_1_25_2","unstructured":"Anti-OVA (DO11.10) T cell receptor (TCR) transgenic lymph node cells (5 \u00d7 10 6 cells) were transferred to BALB\/c mice that were immunized 1 day later with 100-\u03bcg OVA in Freund's complete adjuvant (25). Draining (pool of brachial axillary and inguinal) and nondraining (mesenteric) lymph node cells were isolated 1 to 5 days later and used in MDC chemotaxis assays. The frequency of OVA-specific T cells that migrated was measured with the clonotypic antibody to TCR KJ1-26 (28). Overnight incubation of day 2 draining lymph node cells (at 10 7 cells\/ml) in medium containing interleukin-2 (IL-2) (4 ng\/ml) increased the sensitivity of activated KJ1-26 + cells to MDC (14). Therefore IL-2\u2013cultured cells were used in experiments to detect chemokine production by purified lymph node DCs and stromal cells."},{"key":"e_1_3_1_26_2","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/1074-7613(94)90084-1","volume":"1","author":"Kearney E. R.","year":"1994","unstructured":"Kearney E. R., Pape K. A., Loh D. Y., Jenkins M. K., Immunity 1, 327 (1994);","journal-title":"Immunity"},{"key":"e_1_3_1_26_3","doi-asserted-by":"publisher","DOI":"10.1126\/science.2125367"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.3.447"},{"key":"e_1_3_1_28_2","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.4049\/jimmunol.154.3.1317","volume":"154","author":"MacPherson G. G.","year":"1995","unstructured":"MacPherson G. G., Jenkins C. D., Stein M. J., Edwards C., J. Immunol. 154, 1317 (1995).","journal-title":"J. Immunol."},{"key":"e_1_3_1_29_2","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1084\/jem.157.4.1149","volume":"157","author":"Haskins K.","year":"1983","unstructured":"Haskins K., et al., J. Exp. Med. 157, 1149 (1983).","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_30_2","unstructured":"We thank R. Locksley S. Luther K. Reif and A. Weiss for comments on the manuscript; M. Ansel for help with the in vivo transfer experiments; and C. McArthur for cell sorting. Supported in part by NIH grant AI-40098 the Pew Foundation (J.G.C.) and the American Lung Association (H.L.T.)."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.284.5415.819","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T09:19:35Z","timestamp":1705137575000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.284.5415.819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,4,30]]},"references-count":41,"journal-issue":{"issue":"5415","published-print":{"date-parts":[[1999,4,30]]}},"alternative-id":["10.1126\/science.284.5415.819"],"URL":"https:\/\/doi.org\/10.1126\/science.284.5415.819","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,4,30]]}}}