Infection and Immunity, January 2002, p. 177-184, Vol. 70, No. 1
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.70.1.177-184.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Central Role for Interleukin-4 in Regulating Nitric Oxide-Mediated Inhibition of T-Cell Proliferation and Gamma Interferon Production in Schistosomiasis
Elisabeth A. Patton,,
Anne C. La Flamme,,
Joao A. Pedras-Vasoncelos,,
and Edward J. Pearce*
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853
Received 30 March 2001/
Returned for modification 14 May 2001/
Accepted 11 October 2001
Schistosoma mansoni-infected wild-type (WT) mice develop a Th2 response and chronic disease. In contrast, infected interleukin-4 double-deficient (IL-4-/-) mice develop a Th1-like response and an acute, lethal syndrome. Disease severity in these animals correlates with excessive and prolonged production of nitric oxide (NO) associated with enhanced antigen-driven gamma interferon (IFN-
) production in the absence of IL-4. Strikingly, splenic lymphocytes from infected IL-4-/- mice failed to proliferate as well as those from infected WT mice following stimulation in vitro with antigen or anti-CD3 antibody. Contrary to antigen-driven IFN-
responses, anti-CD3 antibody stimulation of splenocytes resulted in significantly less IFN-
being produced by CD8 cells from infected IL-4-/- mice than by those from infected WT mice or normal mice. NO is largely responsible for the impaired T-cell functions in infected IL-4-/- mice, as inhibition of iNOS significantly enhanced proliferation and IFN-
production.
* Corresponding author. Present address: Department of Pathobiology, University of Pennsylvania, 203D Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19106-6076. Phone: (215) 573-3493. Fax: (215) 898-9557. E-mail: Ejpearce{at}mail.med.upenn.edu.
Editor: J. M. Mansfield
Present address: School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wis.
Present address: School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
Present address: NRC-IBS, Ottawa, Ontario K1K-0R6, Canada.
Infection and Immunity, January 2002, p. 177-184, Vol. 70, No. 1
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.70.1.177-184.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
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Copyright © 2002 by the American Society for Microbiology. All rights reserved.