{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:38:18Z","timestamp":1790303898641,"version":"4.1.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2002,11,1]],"date-time":"2002-11-01T00:00:00Z","timestamp":1036108800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2002,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>CpG oligodeoxynucleotides (CpG ODNs) are known to induce type 1 T-helper-cell (Th1) responses. We have previously demonstrated that CpG ODNs administered during sensitization prevent Th2-mediated eosinophilic airway inflammation in vivo. We also reported that key Th1 cytokines, gamma interferon (IFN-\u03b3) and interleukin 12 (IL-12), are not necessary for this protection. Recent in vivo data suggest that CpG ODNs might also reverse established pulmonary eosinophilia. In order to clarify how CpG ODNs can inhibit established Th2 responses, we evaluated the cytokine production from splenocytes from antigen- and alum-immunized mice. Restimulation with antigen induced IL-5, which was clearly inhibited by coculture with CpG ODNs in a concentration-dependent manner. CpG ODNs also induced IFN-\u03b3, but in a concentration-independent manner. The inhibition of IL-5 production was not mediated through natural killer cells or via CD8<jats:sup>+<\/jats:sup>T lymphocytes. Although IFN-\u03b3 plays an important role in inhibition of antigen-induced IL-5 production by CpG ODNs, IFN-\u03b3 was not the sole factor in IL-5 inhibition. CpG ODNs also induced IL-10, and this induction correlated well with IL-5 inhibition. Elimination of IL-10 reduced the anti-IL-5 effect of CpG ODNs, although incompletely. This may be because IFN-\u03b3, induced by CpG ODNs, is also inhibited by IL-10, serving as a homeostatic mechanism for the Th1-Th2 balance. Overproduction of IFN-\u03b3 was downregulated by CpG ODN-induced IL-10 via modulation of IL-12 production. These data suggest that CpG ODNs may inhibit established Th2 immune responses through IFN-\u03b3 and IL-10 production, the latter serving to regulate excessive Th1 bias. These properties of CpG ODNs might be a useful feature in the development of immunotherapy adjuvants against allergic diseases such as asthma.<\/jats:p>","DOI":"10.1128\/cdli.9.6.1260-1269.2002","type":"journal-article","created":{"date-parts":[[2002,11,1]],"date-time":"2002-11-01T19:04:24Z","timestamp":1036177464000},"page":"1260-1269","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Immunomodulatory Effects of CpG Oligodeoxynucleotides on Established Th2 Responses"],"prefix":"10.1128","volume":"9","author":[{"given":"Kunihiko","family":"Kitagaki","sequence":"first","affiliation":[{"name":"Department of Medicine, Roy J. and Lucille Carver College of Medicine, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vipul V.","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Medicine, Roy J. and Lucille Carver College of Medicine, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Businga","sequence":"additional","affiliation":[{"name":"Department of Medicine, Roy J. and Lucille Carver College of Medicine, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iftikhar","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Medicine, Roy J. and Lucille Carver College of Medicine, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel N.","family":"Kline","sequence":"additional","affiliation":[{"name":"Department of Medicine, Roy J. and Lucille Carver College of Medicine, University of Iowa, Iowa City, Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"969","volume":"151","year":"1995","unstructured":"Abramson, M. J., R. M. Puy, and J. M. Weiner. 1995. Is allergen immunotherapy effective in asthma? A meta-analysis of randomized controlled trials. Am. J. Respir. Crit. Care Med.151:969-974.","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1172\/JCI2250","volume":"102","year":"1998","unstructured":"Akdis, C. A., T. Blesken, M. Akdis, B. Wuthrich, and K. Blaser. 1998. Role of interleukin 10 in specific immunotherapy. J. Clin. Investig.102:98-106.","journal-title":"J. Clin. Investig."},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"6889","DOI":"10.4049\/jimmunol.165.12.6889","volume":"165","year":"2000","unstructured":"Askew, D., R. S. Chu, A. M. Krieg, and C. V. Harding. 2000. CpG DNA induces maturation of dendritic cells with distinct effects on nascent and recycling MHC-II antigen-processing mechanisms. J. Immunol.165:6889-6895.","journal-title":"J. Immunol."},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1042\/cs0940557","volume":"94","year":"1998","unstructured":"Barnes, P. J. 1998. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin. Sci. (London)94:557-572.","journal-title":"Clin. Sci. (London)"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"S466","DOI":"10.1016\/S0091-6749(00)90044-7","volume":"105","year":"2000","unstructured":"Beasley, R., J. Crane, C. K. Lai, and N. Pearce. 2000. Prevalence and etiology of asthma. J. Allergy Clin. Immunol.105:S466-S472.","journal-title":"J. Allergy Clin. Immunol."},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/eji.1830270513","volume":"27","year":"1997","unstructured":"Bellinghausen, I., G. Metz, A. H. Enk, S. Christmann, J. Knop, and J. Saloga. 1997. Insect venom immunotherapy induces interleukin-10 production and a Th2-to-Th1 shift, and changes surface marker expression in venom-allergic subjects. Eur. J. Immunol.27:1131-1139.","journal-title":"Eur. J. Immunol."},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0091-6749(98)70238-6","volume":"101","year":"1998","unstructured":"Borish, L. 1998. IL-10: evolving concepts. J. Allergy Clin. Immunol.101:293-297.","journal-title":"J. Allergy Clin. Immunol."},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"7054","DOI":"10.4049\/jimmunol.161.12.7054","volume":"161","year":"1998","unstructured":"Broide, D., J. Schwarze, H. Tighe, T. Gifford, M. D. Nguyen, S. Malek, J. Van Uden, E. Martin-Orozco, E. W. Gelfand, and E. Raz. 1998. Immunostimulatory DNA sequences inhibit IL-5, eosinophilic inflammation, and airway hyperresponsiveness in mice. J. Immunol.161:7054-7062.","journal-title":"J. Immunol."},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1067\/mai.2001.118795","volume":"108","year":"2001","unstructured":"Broide, D. H., G. Stachnick, D. Castaneda, J. Nayar, M. Miller, J. Cho, M. Rodriquez, M. Roman, and E. Raz. 2001. Immunostimulatory DNA mediates inhibition of eosinophilic inflammation and airway hyperreactivity independent of natural killer cells in vivo. J. Allergy Clin. Immunol.108:759-763.","journal-title":"J. Allergy Clin. Immunol."},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1006\/clin.1997.4380","volume":"84","year":"1997","unstructured":"Chace, J. H., N. A. Hooker, K. L. Mildenstein, A. M. Krieg, and J. S. Cowdery. 1997. Bacterial DNA-induced NK cell IFN-gamma production is dependent on macrophage secretion of IL-12 Clin. Immunol. Immunopathol.84:185-193.","journal-title":"Immunol. Immunopathol."},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"973","DOI":"10.4049\/jimmunol.164.2.973","volume":"164","year":"2000","unstructured":"Chiaramonte, M. G., M. Hesse, A. W. Cheever, and T. A. Wynn. 2000. CpG oligonucleotides can prophylactically immunize against Th2-mediated schistosome egg-induced pathology by an IL-12-independent mechanism. J. Immunol.164:973-985.","journal-title":"J. Immunol."},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1056\/NEJM199602223340804","volume":"334","year":"1996","unstructured":"Creticos, P. S., C. E. Reed, P. S. Norman, J. Khoury, N. F. Adkinson, Jr., C. R. Buncher, W. W. Busse, R. K. Bush, J. Gadde, J. T. Li, et al. 1996. Ragweed immunotherapy in adult asthma. N. Engl. J. Med.334:501-506.","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"7082","DOI":"10.4049\/jimmunol.166.12.7082","volume":"166","year":"2001","unstructured":"Dalpke, A. H., S. Opper, S. Zimmermann, and K. Heeg. 2001. Suppressors of cytokine signaling (SOCS)-1 and SOCS-3 are induced by CpG-DNA and modulate cytokine responses in APCs. J. Immunol.166:7082-7089.","journal-title":"J. Immunol."},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"353","DOI":"10.4049\/jimmunol.150.2.353","volume":"150","year":"1993","unstructured":"Del Prete, G., M. De Carli, F. Almerigogna, M. G. Giudizi, R. Biagiotti, and S. Romagnani. 1993. Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J. Immunol.150:353-360.","journal-title":"J. Immunol."},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.4049\/jimmunol.147.11.3815","volume":"147","year":"1991","unstructured":"Fiorentino, D. F., A. Zlotnik, T. R. Mosmann, M. Howard, and A. O'Garra. 1991. IL-10 inhibits cytokine production by activated macrophages. J. Immunol.147:3815-3822.","journal-title":"J. Immunol."},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1165\/ajrcmb.21.2.3576","volume":"21","year":"1999","unstructured":"Haneda, K., K. Sano, G. Tamura, H. Shirota, Y. Ohkawara, T. Sato, S. Habu, and K. Shirato. 1999. Transforming growth factor-beta secreted from CD4(+) T cells ameliorates antigen-induced eosinophilic inflammation. A novel high-dose tolerance in the trachea. Am. J. Respir. Cell Mol. Biol.21:268-274.","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1172\/JCI5155","volume":"103","year":"1999","unstructured":"Hansen, G., G. Berry, R. H. DeKruyff, and D. T. Umetsu. 1999. Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation. J. Clin. Investig.103:175-183.","journal-title":"J. Clin. Investig."},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1006\/viro.1999.9957","volume":"263","year":"1999","unstructured":"Hassett, D. E., J. Zhang, and J. L. Whitton. 1999. Plasmid DNA vaccines are effective in the absence of IFN gamma. Virology263:175-183.","journal-title":"Virology"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1159\/000024303","volume":"121","year":"2000","unstructured":"Heeg, K., and S. Zimmermann. 2000. CpG DNA as a Th1 trigger. Int. Arch. Allergy Immunol.121:87-97.","journal-title":"Int. Arch. Allergy Immunol."},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/S0167-5699(99)01547-9","volume":"20","year":"1999","unstructured":"Kalinski, P., C. M. Hilkens, E. A. Wierenga, and M. L. Kapsenberg. 1999. T-cell priming by type-1 and type-2 polarized dendritic cells: the concept of a third signal. Immunol. Today20:561-567.","journal-title":"Immunol. Today"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1749-6632.1996.tb32561.x","volume":"796","year":"1996","unstructured":"Kay, A. B. 1996. TH2-type cytokines in asthma. Ann. N. Y. Acad. Sci.796:1-8.","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"L170","DOI":"10.1152\/ajplung.00402.2001","volume":"283","year":"2002","unstructured":"Kline, J. N., K. Kitagaki, T. R. Businga, and V. Jain. 2002. Treatment of established asthma in a murine model using CpG oligodeoxynucleotides. Am. J. Physiol. Lung Cell. Mol. Physiol.283:L170-L179.","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1016\/S0091-6749(99)70022-9","volume":"104","year":"1999","unstructured":"Kline, J. N., A. M. Krieg, T. J. Waldschmidt, Z. K. Ballas, V. Jain, and T. R. Businga. 1999. CpG oligodeoxynucleotides do not require TH1 cytokines to prevent eosinophilic airway inflammation in a murine model of asthma. J. Allergy Clin. Immunol.104:1258-1264.","journal-title":"J. Allergy Clin. Immunol."},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.4049\/jimmunol.160.6.2555","volume":"160","year":"1998","unstructured":"Kline, J. N., T. J. Waldschmidt, T. R. Businga, J. E. Lemish, J. V. Weinstock, P. S. Thorne, and A. M. Krieg. 1998. Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma. J. Immunol.160:2555-2559.","journal-title":"J. Immunol."},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1046\/j.1365-2222.1999.00562.x","volume":"29","year":"1999","unstructured":"Meissner, N., S. Kochs, J. Coutelle, F. Kussebi, C. Baumgarten, H. Lowenstein, G. Kunkel, and H. Renz. 1999. Modified T-cell activation pattern during specific immunotherapy (SIT) in cat-allergic patients. Clin. Exp. Allergy29:618-625.","journal-title":"Clin. Exp. Allergy"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.4049\/jimmunol.136.7.2348","volume":"136","year":"1986","unstructured":"Mosmann, T. R., H. Cherwinski, M. W. Bond, M. A. Giedlin, and R. L. Coffman. 1986. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol.136:2348-2357.","journal-title":"J. Immunol."},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1001\/jama.1969.03160080043009","volume":"208","year":"1969","unstructured":"Mueller, H. L., and M. Lanz. 1969. Hyposensitization with bacterial vaccine in infectious asthma. A double-blind study and a longitudinal study. JAMA208:1379-1383.","journal-title":"JAMA"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.4049\/jimmunol.153.3.1264","volume":"153","year":"1994","unstructured":"Nakajima, H., A. Nakao, Y. Watanabe, S. Yoshida, and I. Iwamoto. 1994. IFN-alpha inhibits antigen-induced eosinophil and CD4+ T cell recruitment into tissue. J. Immunol.153:1264-1270.","journal-title":"J. Immunol."},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/S0091-6749(99)70429-X","volume":"103","year":"1999","unstructured":"Noma, T., and I. Yoshizawa. 1999. IL-12 affects Dermatophagoides farinae-induced IL-4 production by T cells from pediatric patients with mite-sensitive asthma. J. Allergy Clin. Immunol.103:850-858.","journal-title":"J. Allergy Clin. Immunol."},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1046\/j.1365-2222.2000.00700.x","volume":"30","year":"2000","unstructured":"O'Brien, R. M., H. Xu, J. M. Rolland, K. A. Byron, and W. R. Thomas. 2000. Allergen-specific production of interferon-gamma by peripheral blood mononuclear cells and CD8 T cells in allergic disease and following immunotherapy. Clin. Exp. Allergy30:333-340.","journal-title":"Clin. Exp. Allergy"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.4049\/jimmunol.158.8.3666","volume":"158","year":"1997","unstructured":"Oriss, T. B., S. A. McCarthy, B. F. Morel, M. A. Campana, and P. A. Morel. 1997. Crossregulation between T helper cell (Th)1 and Th2: inhibition of Th2 proliferation by IFN-gamma involves interference with IL-1. J. Immunol.158:3666-3672.","journal-title":"J. Immunol."},{"key":"e_1_3_2_33_2","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1172\/JCI7631","volume":"104","year":"1999","unstructured":"Randolph, D. A., R. Stephens, C. J. Carruthers, and D. D. Chaplin. 1999. Cooperation between Th1 and Th2 cells in a murine model of eosinophilic airway inflammation. J. Clin. Investig.104:1021-1029.","journal-title":"J. Clin. Investig."},{"key":"e_1_3_2_34_2","doi-asserted-by":"crossref","first-page":"3930","DOI":"10.4049\/jimmunol.161.8.3930","volume":"161","year":"1998","unstructured":"Redford, T. W., A. K. Yi, C. T. Ward, and A. M. Krieg. 1998. Cyclosporin A enhances IL-12 production by CpG motifs in bacterial DNA and synthetic oligodeoxynucleotides. J. Immunol.161:3930-3935.","journal-title":"J. Immunol."},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1067\/mai.2002.122156","volume":"109","year":"2002","unstructured":"Santeliz, J. V., G. V. Nest, P. Traquina, E. Larsen, and M. Wills-Karp. 2002. Amb a 1-linked CpG oligodeoxynucleotides reverse established airway hyperresponsiveness in a murine model of asthma. J. Allergy Clin. Immunol.109:455-462.","journal-title":"J. Allergy Clin. Immunol."},{"key":"e_1_3_2_36_2","doi-asserted-by":"crossref","first-page":"224","DOI":"10.4049\/jimmunol.163.1.224","volume":"163","year":"1999","unstructured":"Schwartz, D. A., C. L. Wohlford-Lenane, T. J. Quinn, and A. M. Krieg. 1999. Bacterial DNA or oligonucleotides containing unmethylated CpG motifs can minimize lipopolysaccharide-induced inflammation in the lower respiratory tract through an IL-12-dependent pathway. J. Immunol.163:224-231.","journal-title":"J. Immunol."},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"5906","DOI":"10.4049\/jimmunol.165.10.5906","volume":"165","year":"2000","unstructured":"Serebrisky, D., A. A. Teper, C. K. Huang, S. Y. Lee, T. F. Zhang, B. H. Schofield, M. Kattan, H. A. Sampson, and X. M. Li. 2000. CpG oligodeoxynucleotides can reverse Th2-associated allergic airway responses and alter the B7.1\/B7.2 expression in a murine model of asthma. J. Immunol.165:5906-5912.","journal-title":"J. Immunol."},{"key":"e_1_3_2_38_2","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1016\/S0140-6736(96)91617-7","volume":"347","year":"1996","unstructured":"Shaheen, S. O., P. Aaby, A. J. Hall, D. J. Barker, C. B. Heyes, A. W. Shiell, and A. Goudiaby. 1996. Measles and atopy in Guinea-Bissau. Lancet347:1792-1796.","journal-title":"Lancet"},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1126\/science.275.5296.77","volume":"275","year":"1997","unstructured":"Shirakawa, T., T. Enomoto, S. Shimazu, and J. M. Hopkin. 1997. The inverse association between tuberculin responses and atopic disorder. Science275:77-79.","journal-title":"Science"},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1165\/ajrcmb.22.2.3772","volume":"22","year":"2000","unstructured":"Shirota, H., K. Sano, T. Kikuchi, G. Tamura, and K. Shirato. 2000. Regulation of T-helper type 2 cell and airway eosinophilia by transmucosal coadministration of antigen and oligodeoxynucleotides containing CpG motifs. Am. J. Respir. Cell Mol. Biol.22:176-182.","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"e_1_3_2_41_2","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1084\/jem.188.12.2335","volume":"188","year":"1998","unstructured":"Sun, S., X. Zhang, D. F. Tough, and J. Sprent. 1998. Type I interferon-mediated stimulation of T cells by CpG DNA. J. Exp. Med.188:2335-2342.","journal-title":"J. Exp. Med."},{"key":"e_1_3_2_42_2","doi-asserted-by":"crossref","first-page":"6284","DOI":"10.4049\/jimmunol.162.10.6284","volume":"162","year":"1999","unstructured":"Sur, S., J. S. Wild, B. K. Choudhury, N. Sur, R. Alam, and D. M. Klinman. 1999. Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. J. Immunol.162:6284-6293.","journal-title":"J. Immunol."},{"key":"e_1_3_2_43_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1365-2567.2000.00941.x","volume":"99","year":"2000","unstructured":"Tascon, R. E., S. Ragno, D. B. Lowrie, and M. J. Colston. 2000. Immunostimulatory bacterial DNA sequences activate dendritic cells and promote priming and differentiation of CD8+ T cells. Immunology99:1-7.","journal-title":"Immunology"},{"key":"e_1_3_2_44_2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1146\/annurev.iy.13.040195.001343","volume":"13","year":"1995","unstructured":"Trinchieri, G. 1995. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu. Rev. Immunol.13:251-276.","journal-title":"Annu. Rev. Immunol."},{"key":"e_1_3_2_45_2","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1136\/bmj.305.6866.1395","volume":"305","year":"1992","unstructured":"von Mutius, E., C. Fritzsch, S. K. Weiland, G. Roll, and H. Magnussen. 1992. Prevalence of asthma and allergic disorders among children in united Germany: a descriptive comparison. BMJ305:1395-1399.","journal-title":"BMJ"},{"key":"e_1_3_2_46_2","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1136\/bmj.308.6930.692","volume":"308","year":"1994","unstructured":"von Mutius, E., F. D. Martinez, C. Fritzsch, T. Nicolai, P. Reitmeir, and H. H. Thiemann. 1994. Skin test reactivity and number of siblings. BMJ308:692-695.","journal-title":"BMJ"},{"key":"e_1_3_2_47_2","doi-asserted-by":"crossref","first-page":"2701","DOI":"10.4049\/jimmunol.164.5.2701","volume":"164","year":"2000","unstructured":"Wild, J. S., A. Sigounas, N. Sur, M. S. Siddiqui, R. Alam, M. Kurimoto, and S. Sur. 2000. IFN-gamma-inducing factor (IL-18) increases allergic sensitization, serum IgE, Th2 cytokines, and airway eosinophilia in a mouse model of allergic asthma. J. Immunol.164:2701-2710.","journal-title":"J. Immunol."},{"key":"e_1_3_2_48_2","doi-asserted-by":"crossref","first-page":"2644","DOI":"10.1172\/JCI117966","volume":"95","year":"1995","unstructured":"Zuany-Amorim, C., S. Haile, D. Leduc, C. Dumarey, M. Huerre, B. B. Vargaftig, and M. Pretolani. 1995. Interleukin-10 inhibits antigen-induced cellular recruitment into the airways of sensitized mice. J. Clin. Investig.95:2644-2651.","journal-title":"J. Clin. Investig."}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CDLI.9.6.1260-1269.2002","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CDLI.9.6.1260-1269.2002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T05:23:59Z","timestamp":1682400239000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CDLI.9.6.1260-1269.2002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,11]]},"references-count":47,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2002,11]]}},"alternative-id":["10.1128\/CDLI.9.6.1260-1269.2002"],"URL":"https:\/\/doi.org\/10.1128\/cdli.9.6.1260-1269.2002","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,11]]},"assertion":[{"value":"2002-01-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-05-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}