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Inbred mice were infected with<jats:italic>Trypanosoma brucei rhodesiense<\/jats:italic>, and the coordinate stimulation of Th-cell cytokine responses and B-cell responses to the trypanosome variant surface glycoprotein (VSG) was measured. The cytokines produced by T cells in response to VSG, at both the transcript and protein levels, were gamma interferon and interleukin-2 (IL-2) but not IL-4 or IL-5. Isotype profiles of antibodies specific for VSG showed that IgG1, IgG2a, and IgG3 switch responses predominated; no VSG-specific IgE responses were detected. To determine whether cryptic IL-4 responses played a role in promoting the unexpected IgG1 switch response, IL-4 knockout mice were infected; the cytokine responses and Ig isotype profiles of IL-4 knockout mice were identical to those of the wild-type control mice except for dramatically reduced IgG1 levels in response to VSG. Thus, these results revealed an IL-4-dependent component of the VSG-driven B-cell C\u03bc-to-C\u03b31 switch. We speculate that an IL-4 response is mediated primarily by cells other than T lymphocytes since IL-4-secreting but parasite antigen-unresponsive, \u201cbackground\u201d cells were detected in all infected mice and since infected<jats:italic>nude<\/jats:italic>mice also displayed a detectable IgG1 switch response. Overall, our results suggest that B-cell clonal stimulation, maturation, and Ig class switching in African trypanosomiasis may be partially regulated by unusual mechanisms that do not include antigen-specific Th1 or Th2 cells.<\/jats:p>","DOI":"10.1128\/iai.66.2.451-461.1998","type":"journal-article","created":{"date-parts":[[2019,12,31]],"date-time":"2019-12-31T15:22:36Z","timestamp":1577805756000},"page":"451-461","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":48,"title":["Interleukin-4-Dependent Immunoglobulin G1 Isotype Switch in the Presence of a Polarized Antigen-Specific Th1-Cell Response to the Trypanosome Variant Surface Glycoprotein"],"prefix":"10.1128","volume":"66","author":[{"given":"Lisa R.","family":"Schopf","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Bacteriology, University of Wisconsin, Madison, Wisconsin 53706"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"Filutowicz","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Bacteriology, University of Wisconsin, Madison, Wisconsin 53706"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Juan","family":"Bi","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Bacteriology, University of Wisconsin, Madison, Wisconsin 53706"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M.","family":"Mansfield","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Bacteriology, University of Wisconsin, Madison, Wisconsin 53706"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/smim.1993.1050"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"3518","DOI":"10.4049\/jimmunol.157.8.3518","article-title":"Control of parasitemia and survival during Trypanosoma brucei brucei infection is related to strain-dependent ability to produce IL-4.","volume":"157","author":"Bakhiet M.","year":"1996","unstructured":"Bakhiet M. 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