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Infect Immun, February 1998, p. 451-461, Vol. 66, No. 2
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Interleukin-4-Dependent Immunoglobulin G1 Isotype Switch in the Presence of a Polarized Antigen-Specific Th1-Cell Response to the Trypanosome Variant Surface Glycoprotein

Lisa R. Schopf, Hanna Filutowicz, Xiao-Juan Bi, and John M. Mansfield^*

Department of Bacteriology, University of Wisconsin, Madison, Wisconsin 53706

Received 4 September 1997/Returned for modification 21 October 1997/Accepted 10 November 1997

This study examines B-cell immunoglobulin (Ig) class-switching events in the context of parasite antigen-specific Th-cell responses in experimental African trypanosomiasis. Inbred mice were infected with Trypanosoma brucei rhodesiense, 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 Cµ-to-C1 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, "background" cells were detected in all infected mice and since infected nude 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.

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^* Corresponding author. Mailing address: Department of Bacteriology, University of Wisconsin, AHBS Building, 1655 Linden Dr., Madison, WI 53706. Phone: (608) 262-2596. Fax: (608) 265-4899. E-mail: jmm{at}ahabs.wisc.edu.

Present address: Genetics Institute, Andover, MA 01810.

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