{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:52:39Z","timestamp":1790851959004,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2001,3,29]],"date-time":"2001-03-29T00:00:00Z","timestamp":985824000000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2001,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The development of\n                    <jats:italic>in vitro<\/jats:italic>\n                    methods for the identification of skin sensitizers based upon analysis of Langerhans cell (LC) function has been constrained by the fact that these cells represent only a minority population in the skin that, once isolated, alter their phenotype spontaneously and rapidly. Methods have been developed recently that allow the expansion in culture using appropriate cytokine conditions of LC\u2010like dendritic cells (DCs) from certain tissues, including human peripheral blood. It has been demonstrated that culture of human blood\u2010derived LC\u2010like cells with selected potent contact allergens such as 2,4\u2010dinitrofluorobenzene (DNFB) stimulates selective phenotypic changes, including the up\u2010regulation of interleukin 1\u03b2 (IL\u20101\u03b2) mRNA expression, under conditions where skin irritants are without effect. However, in our own previous investigations, we have observed that there appear to be differences between blood donors with respect to the responsiveness of DCs to DNFB\u2010induced changes in IL\u20101\u03b2 expression, differences that could compromise the utility of this approach as a screening method for contact allergens. We have therefore investigated donor variability in DC responsiveness to a panel of known human contact allergens (DNFB; paraphenylene diamine, PPD; methyl\u2010 chloroisothiazolinone\/methylisothiazolinone, CMIT), to the skin irritant benzalkonium chloride and to the mitogen phorbol myristate acetate (PMA). Dendritic cells derived from all donors expressed IL\u20101\u03b2 mRNA constitutively. Treatment of DCs isolated from donors with a responder phenotype to DNFB with PPD or CMIT resulted also in up\u2010regulation of IL\u20101\u03b2 mRNA expression, although such changes were always comparatively modest, generally resulting in a twofold induction compared with vehicle\u2010treated controls. Dendritic cells derived from donors with a non\u2010responder phenotype to DNFB failed also to respond to these additional contact allergens under conditions where the mitogen PMA caused similar increases in IL\u20101\u03b2 expression to those observed for allergen\u2010responsive donors. Benzalkonium chloride failed to provoke changes in the expression of this cytokine in any donor examined, irrespective of their responder phenotype. The temporal stability of the responder\/non\u2010responder DC phenotype was confirmed, with stable phenotypes with respect to DNFB\u2010induced changes in IL\u20101\u03b2 mRNA expression observed over a period of some 18 months. Fifty per cent (6\/12) of donors tested over this period displayed a responder phenotype. These data demonstrate that chemical allergens do stimulate consistent changes in IL\u20101\u03b2 mRNA expression in the proportion of donors who have a responsive phenotype, and that such responses are apparently selective for allergen using the relatively narrow range of materials assessed to date. However, the modest response to very strong contact allergens, coupled with the difficulties of responder\/non\u2010responder phenotypes, means that in its present form this approach does not lend itself to the routine assessment of skin sensitizing activity. Copyright \u00a9 2001 John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/jat.742","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T17:30:12Z","timestamp":1030296612000},"page":"115-121","source":"Crossref","is-referenced-by-count":54,"title":["Allergen\u2010induced changes in interleukin 1\u03b2 (iL\u20101\u03b2) mRNA expression by human blood\u2010derived dendritic cells: inter\u2010individual differences and relevance for sensitization testing"],"prefix":"10.1002","volume":"21","author":[{"given":"Johanna S.","family":"Pichowski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Cumberbatch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Dearman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Basketter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Kimber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,3,29]]},"reference":[{"key":"e_1_2_1_2_2","volume-title":"Allergic Contact Dermatitis in the Guinea Pig","author":"Magnusson B","year":"1970"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1965.01600080079017"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0300-483X(94)90193-7"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-1263(199909\/10)19:5<299::AID-JAT591>3.0.CO;2-C"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-4274(99)00069-7"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(92)90230-P"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.2000.03349.x"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.176.4.1221"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12667296"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1997.00360.x"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004030050422"},{"key":"e_1_2_1_13_2","doi-asserted-by":"crossref","first-page":"3698","DOI":"10.4049\/jimmunol.150.9.3698","article-title":"An essential role for Langerhans cell\u2010derived IL\u20101\u03b2 in the initiation of primary immune responses in the skin","volume":"150","author":"Enk AH","year":"1993","journal-title":"J. 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