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Infection and Immunity, March 2002, p. 1342-1351, Vol. 70, No. 3
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.3.1342-1351.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Control of Experimental Trypanosoma brucei Infections Occurs Independently of Lymphotoxin- Induction

S. Magez,^1* B. Stijlemans,¹ G. Caljon,¹ H.-P. Eugster,² and P. De Baetselier¹

Department of Immunology, Parasitology and Ultrastructure, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Paardenstraat 65, B-1640 Sint Genesius Rode, Belgium,¹ Section of Clinical Immunology, Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland²

Received 6 September 2001/ Returned for modification 9 October 2001/ Accepted 29 November 2001

Trypanosome infections are marked by severe pathological features, including anemia, splenomegaly, and suppression of T-cell proliferation. We have used lymphotoxin--deficient (LT-^-/-) mice, as well as LT--tumor necrosis factor-double-deficient (LT-^-/- TNF^-/-) mice, to analyze the contributions of these related cytokines in both induction of trypanosomosis-associated immunopathology and infection control. Moreover, as the cytokine-deficient mice used have no detectable lymph nodes and lack germinal-center formation upon immune stimulation, we have analyzed the functional importance of both the lymph nodes and spleen during experimental Trypanosoma brucei infections. First, we show that the absence of LT- does not significantly alter early trypanosomosis development or pathology but does result in better control of late-stage parasitemia levels and slightly prolonged survival. This increased survival of infected LT-^-/- mice coincides with the appearance of increased chronic-stage anti-trypanosome immunoglobulin M (IgM)-IgG2a serum titers that are generated in the absence of functional peripheral lymphoid tissue and do not require germinal-center formation. Second, we show that splenectomized mice control their parasitemia to the same extent as fully immune-competent littermates. Finally, using LT-^-/- TNF^-/- double-deficient mice, we show that in these mice T. brucei infections are very well controlled during the chronic infection stage and that infection-induced pathology is minimized. Together, these findings indicate that while increased IgM-IgG2a anti-trypanosome antibody titers (generated in the absence of LT-, peripheral lymph nodes, and germinal-center formation) coincide with improved parasitemia control, it is TNF that has a major impact on trypanosomosis-associated immunopathology.

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* Corresponding author. Mailing address: Department of Immunology, Parasitology and Ultrastructure, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Paardenstraat 65, B-1640 Sint Genesius Rode, Belgium. Phone: 32.2.359.03.01. Fax: 32.2.359.03.59. E-mail: stemagez{at}vub.ac.be.

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Infection and Immunity, March 2002, p. 1342-1351, Vol. 70, No. 3
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.3.1342-1351.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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