{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T07:25:25Z","timestamp":1770103525825,"version":"3.49.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2000,1,1]],"date-time":"2000-01-01T00:00:00Z","timestamp":946684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Using a Schistosoma mansoni egg-induced granuloma model, we examined the ability of CpG oligodeoxynucleotides (ODN) to suppress Th2-type cytokine expression and to prophylactically immunize against Th2-dependent pulmonary pathology. The mechanism was examined by studying Th2 response regulation in cytokine-deficient mice. Surprisingly, our findings revealed several functions of CpG DNA that were completely IL-12 independent. Most striking was the marked suppression in Th2 cytokine expression and granulomatous inflammation observed in egg\/CpG-sensitized IL-12-deficient mice. Immune deviation was not dependent on NK or B cells. However, a role for IL-10, B7.1, and CD40 expression in Th2 response inhibition was suggested. Indeed, CpG ODN up-regulated all three elements in both wild-type and IL-12-deficient mice. The role of IL-10 was demonstrated in mice exhibiting combined deficiencies in IL-12 and IL-10. Here, a marked increase in egg-specific IL-4\/IL-5-producing cells confirmed a role for both cytokines in Th2 response inhibition. Nevertheless, the frequency of Th2-producing cells was again reduced by CpG ODN. However, in marked contrast to IL-12-deficient animals, a significant increase in IFN-\u03b3-producing cells likely explains the reduced Th2 response in IL-10\/IL-12-deficient mice. Thus, a novel IL-12-independent type 1-inducing pathway was revealed in the combined absence of IL-12 and IL-10. Together, these data demonstrate 1) that the Th1-promoting activity of CpG DNA is controlled by IL-12 and IL-10, and 2) that Th2 response inhibition by CpG ODN involves IL-12-independent changes in IL-10 and costimulatory molecule expression. These findings illustrate the utility of CpG DNA as adjuvants for vaccines designed to prevent Th2-dependent immunopathology.<\/jats:p>","DOI":"10.4049\/jimmunol.164.2.973","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:46:15Z","timestamp":1398023175000},"page":"973-985","source":"Crossref","is-referenced-by-count":46,"title":["CpG Oligonucleotides Can Prophylactically Immunize Against Th2-Mediated Schistosome Egg-Induced Pathology by an IL-12-Independent Mechanism"],"prefix":"10.1093","volume":"164","author":[{"given":"Mo\u0301nica G","family":"Chiaramonte","sequence":"first","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Hesse","sequence":"additional","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen W","family":"Cheever","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute , Rockville, MD 20852"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas A","family":"Wynn","sequence":"additional","affiliation":[{"name":"Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,1,15]]},"reference":[{"key":"2026020213160864800_R1","first-page":"955","volume-title":"J. 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